The Red Devils have been hit with the news that new signing Leny Yoro will be missing for the next three months after fracturing his metatarsal during Saturday's pre-season clash with Arsenal.
Rasmus Hojlund, meanwhile, was forced off with a hamstring issue against the Gunners, and the Denmark international is set to be missing for six weeks.
Man United suffered another double injury blow in their fourth friendly of the summer, with Rashford and Antony both limping off against Real Betis.
Rashford scored from the penalty spot in the 18th minute of the clash, but he was substituted in the 62nd minute following a heavy tackle from Sergi Altimira.
Rashford, Antony were forced off against Real Betis
Antony, meanwhile, was introduced in the 62nd minute, but he was unable to complete the match, having picked up an injury late on.
The Brazilian looked frustrated as he headed straight down the tunnel, suggesting that he could now be facing a spell on the sidelines.
Man United will now need to assess the duo; it is believed that Rashford's issue was only an impact injury, but he would still be a doubt for Saturday's final pre-season fixture against Liverpool.
"I think it was okay, the lads did well. At the start we had some problems in getting control and we went 1-0 down which shouldn't happen. I actually think this was the first time they entered our box," Man United head coach Erik ten Hag told reporters after the match.
"But then we took over and we bounced back, I think we made three really good goals, first the penalty and it was a good action from Amad [Diallo]. The second I would [also] say is a very good goal. The third one from the corner is also a nice goal. The second where Harry Amass put the cross [in] and Amad scored the goal with the finish was lovely."
Man United come from behind to win
Iker Losada sent Real Betis ahead in the 15th minute of Saturday's clash, before Rashford, Amad Diallo and Casemiro registered to make it 3-1 to Man United in the 31st minute.
Diego Llorente then scored a second for Real Betis in the 61st minute, but the La Liga outfit were unable to register again.
"This week everyone has to get more minutes in to come [up] to match fitness. Of course the games will get tougher and I think on Saturday it will be a very good test when we face Liverpool. That is very good preparation for the new season," Ten Hag added.
"We bounced back very well and a comfortable win, 3-1 at half-time and I thought our [lead] could have been even higher. That could have been more and even after half-time we created some good chances again.
"Penalty, no penalty, I don't know, I think it is a penalty because [Marcus] Rashy has to drop out [of the game]. We concede with 10 men from the corner and that is also something we have to learn because in the league and in the season we may have to defend a corner with 10."
Man United will round off their US Tour against Liverpool on Saturday before heading back to England to prepare for the Community Shield with Manchester City on August 10.