It was another damaging blow to David Moyes' hopes of getting back into the Premier League's top four, especially after the optimism of Mata's arrival last week.
United weren't helped by early injuries to both Jonny Evans and Phil Jones, but they didn't deserve to beat Stoke, for whom Charlie Adam scored either side of half-time to seal a 2-1 win.
Here are six things we learned from United's defeat on another miserable day for Moyes.
All quotes and reported speech was obtained first-hand.
David Moyes highlighted United's poor luck after the game, and he had a point.
Charlie Adam's free-kick took a horrible deflection to give Stoke the lead, and he lost both his centre-halves before half-time.
At a windy, hostile Britannia Stadium, United were up against it, and they didn't get any luck to help them out.
Moyes was right to point it out after the game because it played a huge part in how the game unfolded.
But there was a sense afterwards that he was trying to hide behind United's misfortune rather than just accept it as a factor in their defeat.
Moyes had already seen Jonny Evans limp off when Phil Jones clashed heads with Jonathan Walters and had to be stretchered off.
With Rafael already on at right-back, Moyes moved Michael Carrick to centre-half—the only logical decision.
But instead of trying to keep United's shape and put Darren Fletcher on in midfield, Moyes put Danny Welbeck on and moved Wayne Rooney into midfield.
It essentially removed Rooney as an attacking threat, and, while he did all right in midfield, United missed him playing further forward.
Juan Mata's arrival at United was greeted with a massive amount of optimism from the fans, and rightly so.
He's a wonderful player and it was a big lift for a team that was in desperate need of something positive.
But defeat at Stoke showed that he can't do it all on his own.
United's key flaw in the centre of midfield was exposed when Carrick moved to centre-half, and it was proof that a wonderful array of attacking talent will not win you every game.
With the transfer window now shut, Moyes is reliant on what he's got, and the result at Stoke was a reminder they won't walk into the top four just because they've got Mata.
There weren't many people inside the Britannia Stadium who thought United had played well, but Moyes insisted afterwards they were the better team.
That was a disservice to Stoke, who deserved to win, even if they needed a bit of luck to do it.
It wasn't until stoppage time in the second-half that United really started to threaten.
Patrice Evra got to the byline a couple of times and Rooney hit the post with a free-kick.
But for Moyes to say United were the better team was misguided. They didn't create nearly enough to win the game.
The defeat at the Britannia Stadium left United six points behind fourth-placed Liverpool, having played a game more.
It's going to take a fantastic run of results in the second half of the season for them to claw their way back into the race for fourth, but there are no signs it's coming.
They had Rooney, Van Persie, Mata and Carrick available against Stoke, their four key players, and were well beaten by a determined, hard-working Stoke side.
Liverpool were comprehensive winners at Stoke, and it's the type of game United have to be winning if they've got any hope of qualifying for next season's Champions League.
Shinji Kagawa wasn't in United's squad at Stoke, and Moyes confirmed afterwards that he wasn't injured.
He has never been a regular this season but his place has come under even more threat with Juan Mata's arrival.
Mata started at Stoke with Adnan Januzaj on the bench, meaning there was no room for Kagawa in the 18-man squad.
If that continues, it will only end in Kagawa leaving Old Trafford at the earliest possible opportunity.