Manchester United defender is facing around a month out with damage to his hamstring suffered in training prior to Sunday's 3-0 thrashing at the hands of Liverpool, according to The Mirror.
Smalling missed the match and forced manager David Moyes to shuffle his pack in central defence, opting for the pairing of Nemanja Vidic and Phil Jones.
Moyes is now expected to be without the England international until mid-April, meaning he has no chance of featuring against Olympiakos in Wednesday night's crunch Champions League last-16 showdown.
With Jonny Evans also sidelined Moyes must choose between Vidic, Jones and Rio Ferdinand for that European clash, with United needing at least a two-goal swing to have any chance of qualifying for the last 16 and keeping ambitions of a Champions League return next season alive.
Vidic will be unavailable for Saturday's Premier League visit to West Ham through suspension though, leaving the Red Devils thread bare domestically as a disastrous campaign threatens to descend into farce.
United also face local rivals Manchester City next week with Vidic definitely ruled out, while fixtures against Aston Villa and Newcastle United come before Smalling's projected return date.