Both men were forced off in the first half of the game a The JJB Stadium and now look set to miss this weekend's crucial local derby with Manchester United.
Howey limped off with a foot injury while Distin sustained a hamstring problem leaving Keegan will all sorts of defensive problems for the United clash.
Their absence will be a major blow to City and Keegan admitted that he wished he had played some of his younger players and rested his senior players for Premiership action.
"I kind of wish we had put the kids in now," said Keegan. "But we treated the match with respect and that was about as strong as we could manage.
"I wanted to win the game but we weren't quite good enough to do that.
"The last 15 minutes was like a proper cup tie but it was too late then.
"But fair dos to Wigan and I wish them all the luck in the world.
"We were found to be a little wanting on the night and picked up two injuries.
"But that means a chance for someone else and we've got to make a plus out of a minus."
Keegan admitted he fears he may be without two of his most influential performers for some time.
"It's a worry because I can't go into the transfer market to do something about it," said Keegan. "Steve is going for an x-ray and Slyvain could be out for a while."
Meanwhile, City are being linked with a move for former Manchester United star Danny Higginbotham.
Keegan is thought to be considering a move for the Derby ace when the transfer window re-opens in January.
Derby could be willing to sell the highly-rated defender to bring in much-needed funds and he could be available at a knock-down price of £1.5 million.
Rams boss John Gregory has admitted that he will be forced to sell a number of players in January to ease the club's crippling debts.
"Money has to be raised somehow and that is likely to mean that players will be sold in January
