Andrew Johnson, Fitz Hall, Vassilis Lakis and Wayne Routledge are struggling with injuries or illness and are unlikely to feature. Gonzalo Sorondo is out for at least a month with a hamstring problem.
Others, including Emmerson Boyce, Michael Hughes and Aki Riihilahti, are also set to be rested.
United's policy has long been to rest star names in the competition, but Sir Alex Ferguson can call on internationals such as Phil Neville, Tim Howard and Wes Brown as well as blooding youngsters tonight.
A Football League spokesman said: "We understand that football is about a squad system but managers will put out teams they think will win the game."
