Manchester United boss Louis van Gaal was forced into an early change against Southampton as Chris Smalling limped off with a leg problem.
As reported by Goal.com, the United defender dropped to the ground after just 17 minutes and gestured to the bench that he couldn't continue. It followed a collision with Southampton forward Graziano Pelle.
Jonny Evans replaced Smalling in the centre of United's defence, as the Northern Irishman has recently returned to the Old Trafford set-up following an injury of his own.
Louis van Gaal had started with Smalling alongside Marcos Rojo and Paddy McNair, but the young academy graduate was also replaced before the half time interval as Van Gaal shuffled his pack early on.
Ander Herrera was brought on to replace McNair in a tactical change after 38 minutes, as McNair had endured a torrid time.
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Smalling adds to Van Gaal's injury troubles, as he joins the likes of Luke Shaw, Rafael da Silva and Phil Jones on the treatment table.
More positively for Van Gaal, Jones and Rafael should be returning to fitness sooner rather than later as they step up their recoveries with light training.
The loss of Smalling is a big one though, especially if the England defender is absent for any length of time. Michael Carrick deputised against the Saints but he is a centre midfielder and Van Gaal will want him in his best position.
Smalling has suffered an injury-hit season so far, like many of United's defenders, having dealt with groin and thigh issues already this campaign. Ill discipline in the Manchester derby also cost Smalling through suspension.