Southampton will miss Charlie Austin for at least two months after the striker suffered a hamstring injury.
Austin suffered the problem last weekend against Huddersfield, limping off the pitch with 11 minutes remaining.
He has scored five goals in his last seven Premier League games, but was already serving a three-match ban for violent conduct for a kick to the face of Huddersfield goalkeeper Jonas Lossl.
Manager Mauricio Pellegrino said Saints were awaiting the results of a scan, but said he did not expect a quick recovery.
"Charlie will be out more than normal. He will have another test to analyse a little bit better his injury, the grade of his injury," Pellegrino said.
"We will see but I expect Charlie will be out for a couple of months minimum. It's a big pity because Charlie was in a really good moment."
Fans booed Southampton after the 5-2 Boxing Day collapse before Tottenham at Wembley and Saints have not won since Nov. 26, the intervening seven games marred by four defeats.
Manchester United await at Old Trafford on Saturday and while under-pressure Pellegrino understands the supporters' frustrations, he insists there is plenty of opportunity left to climb away from the relegation zone.
"Everybody that works at the top level works under the opinion of everybody. I respect those opinions and I have the same feeling as the fans," Pellegrino said. "I'm not happy when we don't play well and I would like to keep the people proud of our team.
"But almost 50 percent of the Premier League is ahead and we still have time to bounce back and show another side.
"For sure we can turn this around. Spurs played well and we were really poor defensively. When you're poor defensively, they [opponents] look more than normal.
"For this reason we have to come back to simple principles and come back in our performance.
"Manchester United are a powerful team, but we are in the moment that we have to think more about us and what we have to do on the pitch. This is our reality and can't talk about the other teams.
"Even for Manchester United it is difficult to win many games in a row because the Premier League is really competitive. Everybody is suffering this."