Sir Alex Ferguson is facing up to at least three weeks without any of his first choice back line, while there are fears that some of those players could be sidelined for 10 weeks.
United went into their opening Premier League fixture without full-backs Rafael - who dislocated his shoulder in training on Friday - and Patrice Evra who lost his battle with a knee problem.
Young, but ready: Chris Smalling is confident he and Phil Jones can fill in for the injured duo of Nemanja Vidic and Rio Ferdinand
And to compound problems, Nemanja Vidic and Rio Ferdinand both hobbled off against West Brom with the latter expected to miss a month and a half, more than twice that of the Serb.
United face successive home games against north London duo Arsenal and Tottenham in the coming weeks. But 21-year-old is Smalling is adamant he and teenage partner Jones can fill in.
The former Fulham man said: 'It's unfortunate to see your big players go down injured. But the manager has shown all pre-season he's willing to give the young players a go and he's thrown them in to big games.
Double trouble: Vidic and Ferdinand are set to miss three and six weeks respectively
'So it's great to see them step up. Everyone's really gelling and with Jonny (Evans) and people coming in like Fabio, it's great to see.
'If you do well, the manager will keep you in the team. It's a big marker to the other players and the rest of the squad that, if you play well, it doesn't matter how old you are. If you've got that ability, the manager is going to put you in.
'Phil and I have played in pre-season, swapping centre-back and right-back as the manager wants us to show we can play in those two different positions when people are injured.
'I'd rather play centre-back as it's my main position - it's where I will aim to play many of my games this season. But the manager feels I can help in there, if and when I'm needed.'
CLICK HERE TO SIGN UP FOR OUR FREE FANTASY FOOTBALL GAMELindegaard ready to be United's No 1 after De Gea's poor start at Old TraffordDon't worry! De Gea will shine, claims former United legend SchmeichelYoung calls on United to use West Brom win as inspiration for title defence