Teenage forward Powell, on loan from City's rivals Manchester United, has not played since January due to a hamstring problem and only returned to full training on Friday.
Ben Watson, whose late headed goal defeated City at Wembley last May, is out for the season after sustaining a double fracture in his leg while Martyn Waghorn, Ryan Tunnicliffe and Rob Kiernan are all cup-tied.
Latics boss and City cult hero Uwe Rosler may unleash winger Callum McManaman (ankle) for the first time since the last round when Wigan beat Cardiff.
Long-term injury victims Scott Carson (thigh), Gary Caldwell (calf) and Shaun Maloney (hip) are all back in training, although this clash is likely to come too soon for each of them.