Last season's top two will do battle on just the second weekend of the new campaign when champions Leicester City welcome Arsenal to the King Power Stadium on Saturday evening.
Both teams suffered defeats on the opening weekend and will be looking to bounce back from that with a substantial scalp to kick-start their seasons.
Leicester
If Leicester were still in dreamland following their phenomenal achievements from last season, they were swiftly brought back to earth with a bump on the opening weekend.
After a 2015-16 campaign littered with surprises - with Leicester sensationally leading the way - there was a sense of irony in the Foxes being the ones stunned in the very first game of the new season when they fell to a 2-1 defeat at the hands of troubled Hull City.
Many were sceptical of Leicester's chances of maintaining their place amongst the Premier League's elite during the upcoming campaign, but the champions were at least expected to get their defence off to a winning start against a newly-promoted side with only 13 fit players and a caretaker manager in charge.
As it was, they became the first Premier League champions to lose the opening game of their title defence as goals from Adama Diomande and Robert Snodgrass either side of a Riyad Mahrez penalty made the difference.
Claudio Ranieri had warned throughout the summer that things would be even more difficult for his side this season, and the opening-day performance suggested that his primary target of reaching 40 points and Premier League survival is perhaps not as cautious as it first appeared.
However, this is still a Leicester side who have lost just five of their last 48 Premier League outings and who have managed to keep the majority of their title-winning side together - with the exception of N'Golo Kante.
The biggest remaining question mark heading into the new season surrounded the future of Mahrez, but the Algerian's decision to sign a new four-year deal means that Ranieri can now afford to focus solely on matters on the pitch.
The Foxes were beaten just once on home turf throughout the 2015-16 campaign, although that loss did come at the hands of Arsenal last September as Leicester's unbeaten start to the season came to an end.
Recent form: L
Arsenal
No team has done false starts quite like Arsenal in recent seasons. Perennial title hopefuls and top-four mainstays, the Gunners have now lost their opening game in three of the last four campaigns - all at home.
The latest of those came in a thrilling contest with Liverpool on Sunday as Arsenal conceded four goals in the space of 20 minutes either side of half time on their way to a 4-3 defeat.
The Gunners had looked in control until Philippe Coutinho's stunning free kick right on the stroke of half time, while goals from Alex Oxlade-Chamberlain and Calum Chambers gave them hope of a comeback from 4-1 down, but ultimately they fell just short.
It was the last thing that Arsene Wenger needed following a summer of inactivity, and sure enough the final whistle sparked derision from the home fans as Arsenal's season began on a sour note.
On paper, there should have been cause for optimism following last season as Arsenal recorded their highest finish in the Premier League for more than a decade, but in reality they never seriously challenged Leicester in the closing stages of a campaign that smacked of missed opportunity.
The summer transfer window has hardly done much to raise optimism among frustrated fans, with the early arrival of Granit Xhaka only being followed by Rob Holding, leaving Arsenal still short at both ends of the field.
It is in defence where their main problems lie, and it could once again be a makeshift back four this weekend as Wenger has so far failed to bring in reinforcements, while injuries to Aaron Ramsey and Alex Iwobi in their season opener have not helped matters.
Should Leicester's attack perform like they did throughout last season then the Gunners will be in real danger of losing their opening two league games for the first time under Wenger and the first time since the inaugural Premier League season in 1992-93.
Such a result would also heap the pressure on Wenger at a very early stage of the season, and leave them potentially six points behind the frontrunners after only two games.
Recent form: L
Team News
Ramsey returned to action earlier than the other players who reached the latter stages of Euro 2016, and that appears to have backfired after he was ruled out for a month with a hamstring strain.
Iwobi is sidelined for a similar period following the opening day, and the pair join a substantial list of Arsenal absentees heading into the new season.
Injuries to Per Mertesacker and Gabriel Paulista mean that Chambers and Holding may once again provide an inexperienced centre-back partnership, although Laurent Koscielny could be rushed back following his extended break after the Euros.
Questions remain over the French defender's match fitness, but Wenger is thought to be considering including him along with Olivier Giroud and Mesut Ozil.
Xhaka will be hopeful of making his first start for the club, while Oxlade-Chamberlain, Santi Cazorla and Jack Wilshere are also pushing for inclusion in the starting XI.
Leicester, meanwhile, have no new injury concerns following the opening weekend, but are still without the suspended Robert Huth.
Luis Hernandez is expected to fill in for the centre-back alongside Wes Morgan once again, while fellow new signing Ahmed Musa should also retain his place up front alongside Jamie Vardy, who turned down a move to the Gunners during the summer.
Leicester possible starting lineup:
Schmeichel; Simpson, Hernandez, Morgan, Fuchs; Mahrez, Mendy, Drinkwater, Gray; Musa, Vardy
Arsenal possible starting lineup:
Cech; Bellerin, Koscielny, Chambers, Monreal; Xhaka, Elneny, Walcott, Cazorla, Sanchez; Giroud
Head To Head
It may have been a disappointing 2015-16 campaign for Arsenal, but they were the only side to do the double over Leicester last season, winning 5-2 at the King Power in September before striking late to edge a 2-1 victory in February.
That continued Arsenal's dominance of this fixture in recent years, with Leicester having failed to win any of their last 19 Premier League meetings with the Gunners (D6 L13) - the joint-longest active run in the top flight.
Leicester have kept just one clean sheet in their last 27 league games against Arsenal, while this weekend's visitors have never lost a Premier League away game at the King Power Stadium.
We say: Leicester 2-2 Arsenal
Last weekend was the first time that the top two from the previous English top-flight season have both lost their opening games since 1953-54, and both will be desperate to get off the mark at the second time of asking. This fixture usually provides goals and, with both teams not at full strength defensively, we can see that happening again on Saturday. Neither looked particularly impressive in their first outings, though, so this one could end all square.