Doncaster striker Billy Sharp will miss the clash after being diagnosed with ankle ligament damage.
The forward sustained the injury during Saturday's 2-1 defeat at Brighton and a scan on Monday showed up the damage, but Rovers are hopeful that surgery will not be required.
Fellow forward James Hayter suffered a knee injury at Brighton and will join a Sharp on a lengthy casualty list.
Already out injured are James O'Connor, James Chambers, Martin Woods, Brian Stock, Adam Lockwood, Shelton Martis and Mark Wilson.
Tranmere manager Les Parry is hoping to be able to call on striker Enoch Showunmi.
The forward missed Saturday's 1-0 win over Chesterfield with a shin injury but returned to training on Monday and could yet be passed fit to face Sean O'Driscoll's men.
Parry has no other major concerns as his men seek to build on their morale-boosting victory over the League Two champions at the weekend.
It was a performance which filled Parry with confidence ahead of the trip to the Keepmoat Stadium to face Championship opposition.
The Rovers boss said: "It was nice keeping the clean sheet and winning the game was extra nice. It was the perfect result."