The midfielder came off the bench in the League One defeat to Ipswich for his first appearance after a three-month injury layoff but pulled his quad, meaning he faces another three weeks on the sidelines.
However, Scott Davies, Mark Ellis and Evan Gumbs all remain out for a fixture which was rescheduled for Thursday because of a waterlogged pitch last week. Tranmere hit back from 3-0 down to draw 3-3 at Vicarage Road earlier this month to force a replay.
Watford boss Nigel Pearson is set to once again rotate his team following a congested fixture schedule.
Midfielder Nathaniel Chalobah is a doubt after a hip problem forced him off during the closing stages of the Premier League defeat at Aston Villa on Tuesday night, while forward Ismaila Sarr (hamstring) is another unlikely to feature.
Several under-23 players are expected to be drafted in for the cup tie – including goalkeeper Daniel Bachmann, teenage defender Bayli Spencer-Adams and midfielders Domingos Quina and Tom Dele-Bashiru, while forwards Isaac Success and Andre Gray should also be involved again.
Striker Danny Welbeck is closing in on a return from a hamstring problem. Tom Cleverley (foot), Daryl Janmaat (knee), Will Hughes (groin), Kiko Femenia (thigh) and Sebastian Prodl (hamstring) all continue their own rehabilitation.