Kyle McFadzean, Hope Akpan, Gary Alexander and Nicky Ajose should return to the Crawley line-up.
Defender McFadzean, midfielder Akpan, skipper Alexander and fellow striker Ajose were rested as manager Richie Barker made six changes for Tuesday's 3-2 Johnstone's Paint Trophy win over Gillingham.
Town have no new injury worries but centre-half Claude Davis (hip) and winger Sergio Torres (leg) were sidelined in midweek and are set to miss out again.
Mike Jones, the recent signing from Sheffield Wednesday, hopes to keep his place after making his full debut against the Gills although fellow midfielder Scott Neilson pushed his claims for a spot in the starting line-up by climbing off the bench to hit the winner.
Portsmouth's threadbare squad will be missing Paul Connolly, Mustapha Dumbuya, Conor Clifford and Jordan Obita when they head to Sussex.
Defender Connolly aggravated a groin injury during the midweek Johnstone's Paint Trophy penalty shoot-out win over Bournemouth which could cut short his loan spell from Leeds.
Full-back Dumbuya is on international duty with Sierra Leone and on-loan Chelsea midfielder Clifford will be linking up with the Republic of Ireland Under-21s.
Winger Obita is also out as he serves the second game of a three-match ban for his red card against Oldham last Saturday.
But midfielder Lee Williamson made a welcome return as a substitute against the Cherries after a hamstring problem and is set to be involved again.