Bothroyd, who hurt his ankle during the recent home defeat to Watford, sat out last week's defeat at Cardiff and is not likely to feature.
Stoke loanee Mamady Sidibe partnered Chris O'Grady up front at Cardiff but is also doubtful due to a hamstring strain, while defender Anthony Gardner is struggling with a similar problem. Both players will undergo late fitness tests.
Gary Madine and Rodri are on stand-by should Sidibe fail to make it, while Kieran Lee and Daniel Jones provide manager Dave Jones with alternative options at the back.
Midfielder Danny Mayor is hoping to retain his place in the starting line-up after making his full-debut for the club at Cardiff, while David Prutton is expected to continue alongside him after he made his first appearance for the Owls last week following his return from a loan spell Scunthorpe.
Wednesday, who have lost their last six league matches, are hoping to climb out of the bottom three with victory.