Quadruple world champion Sebastian Vettel needs a "really good season" to get his F1 career back on track.
Now 32, the German driver has struggled more recently at Ferrari, but Marko effectively rules out a return to Red Bull for Vettel "for very simple monetary reasons".
"We cannot afford two such top stars," Marko told Sky Deutschland, also referring to Max Verstappen who has just been signed up through 2023.
"If he (Vettel) wants to keep going and wants to continue to have a well-paid contract with a competitive team, he has to have a really good season this year," Marko, 76, added.
"Charles Leclerc has ensured that Sebastian has lost his number 1 status, however he is and remains a four-time world champion. But it will not be as easy for him as it was with us, because his car is not dominant.
"He will have to leave his comfort zone," Marko said.
2016 world champion Nico Rosberg agrees, telling RTL: "It's not easy for Sebastian, because Leclerc is the one who got the strong commitment from the team.
"But there is also a reason for that, as Sebastian has not had optimal seasons in the past few years.
"What he has to do now is regain 100 percent trust from his team. Especially in the first races, it's really important that he performs well," Rosberg added.
Ferrari boss Mattia Binotto has hinted that Vettel could stay in 2021, but that could be as a de-facto number 2 driver only.
"I am convinced that we have the strongest pair of drivers, even if they sometimes cause trouble for us," Binotto, referring to Vettel and Leclerc, smiled to Rai 2.