The incident occurred near the end of the opening period when Rooney fired a low cross from Michael Carrick just over the crossbar.
In attempting to make a tackle, Michael Duberry accidentally trod on Rooney's foot.
It was clear instantly Rooney had a problem, as he went down and removed his boot.
Although he was able to continue briefly, he did not reappear for the second half, with Sir Alex Ferguson sending the 21-year-old for a scan.
Although the United boss expressed the hope the damage would not be too bad, his worst fears now appear to have been confirmed, although the precise extent of the injury is not known.
Ferguson said: "There was no point in him continuing because there was a lot of swelling and he had quite a lot of pain.
"If Wayne had stayed on, we would have gone on to win the match.
"That lack of a central striker cost us."