Simek missed much of last year with ankle and hamstring injuries but played 70 minutes for the reserves on Wednesday.
Lewis Buxton misses out through suspension, so the returning Richard Hinds could continue at right-back.
Wednesday will give fitness tests to Richard Wood (knee), Mark Beevers (ankle) and Tommy Spurr (hip), but all are expected to feature.
Boss Brian Laws has hinted at changes after the disappointing 1-0 home defeat to Barnsley in midweek.
That could mean possible starts for Francis Jeffers, Sean McAllister and Wade Small as the Owls bid to recover from successive defeats against the Tykes and Doncaster.
Nick Carle returns to the Crystal Palace squad for the trip.
The Australian midfielder missed Tuesday night's 3-1 win at Plymouth due to a one-match ban.
But winger Paul Ifill faces a late fitness check after suffering a slight hamstring injury at Home Park.
Ifill played up front alongside Alan Lee in midweek and boss Neil Warnock could stick stick with the 4-4-2 formation, with Victor Moses and Shefki Kuqi his other options in attack.
Claude Davis will keep his place at the back after a successful debut at Plymouth, having now extended his loan spell from Derby until the end of the season.
Defender Paddy McCarthy (shoulder) remains the only injury absentee while midfielder Carl Fletcher is joining Plymouth on loan.
Sporting Life