Smalling faces three months on the sidelines after suffering a broken metatarsal in training on Wednesday having stayed at home during United's pre-season tour as he looked to complete his recover from the groin injury that sidelined him last season.
The 21-year-old is set to miss United's first half dozen Premier League games and their opening Champions League salvos, in addition to a likely England call-up for next month's friendly with Italy in Berne and the World Cup qualifiers beyond. Ferguson said: "It is a bad blow for the boy because he missed the end of the season with a groin injury."
He added: "We thought we had him on the right road to recovery and he gets another injury, which is bad news. He got it in training on Wednesday, was diagnosed on Thursday and we decided to operate last night. Normally with a metatarsal you are looking at between 10 weeks and three months. He is only 21. He is young. Hopefully he gets over it."
If there is any consolation it is that with skipper Nemanja Vidic set to return from a cruciate operation during the second stage of United's pre-season and Phil Jones also available, Ferguson does have options even if Jonny Evans is unlikely to be fit for the opening trip to Everton on August 20.
Not that they looked very convincing on Saturday, when it took a last-minute equaliser from Bebe of all people to avoid an embarrassing defeat to Ajax Cape Town. United have had few players who have been maligned quite as much as Bebe, bought for £7million, by Ferguson's admission, without actually watching him play.
For virtually all of that time, he has appeared a very expensive mistake. An attempt to inject some confidence into the Portugal Under-21 striker by sending him out on loan to Besiktas last year ended within weeks when he suffered a ruptured cruciate knee ligament.
And whilst he did not do that much following his second-half introduction into the 1-1 draw at Green Point Stadium, Bebe took his goal well enough.
"That was his first game for eight months," said Ferguson. "His recovery is complete and he started training with us on July 5.
"He will be pleased to be back playing and pleased he scored a goal. We will wait and see how the season progresses for him. It does give me a headache the number of strikers I have got. But it is not the biggest problem."