Bothroyd, who had far and away his best game in a Wednesday shirt against Leeds on Friday night, has been unwell and having tests on a stomach problem.
Chris Kirkland will be back in action after being assaulted on the pitch by a Leeds fan in the derby clash and former Everton keeper Adam Davies is on the bench after joining the Owls on a month-to-month basis. Davies was released by the Goodison club at the end of last season and takes his place with Stephen Bywater (pneumonia) and Arron Jamieson (groin) both ruled out.
Joe Mattock should be back in the squad after suffering a virus but Rhys McCabe is likely to be out with a thigh injury.
Wednesday go into the match looking for their first league win in two months against managerless Blackburn.