Victor Wanyama's hamstring injury marred Southampton's FA Cup third-round replay win at Ipswich for manager Ronald Koeman.
Saints arrived at Portman Road riding the crest of a wave following Sunday's impressive victory at Manchester United.
That win came at a cost, though, with influential centre-back Toby Alderweireld sustaining a hamstring strain which will see him miss up to four weeks.
It means Saints now have just two centre-backs available, while their defensive midfield options have been depleted by injuries to Morgan Schneiderlin and Wanyama. An adductor strain saw France midfielder Schneiderlin miss the 1-0 win at Ipswich last night - a match which saw Wanyama pull up with a hamstring injury just before half-time.
"It is really negative because already we have some other injuries," Koeman said. "I already spoke before the game with Victor and Steven Davis as I had made the decision to give both players 45 minutes. Then 12 seconds before half-time, he got his hamstring injury and, okay, you know if it is really a hamstring injury then he will be out for four or five weeks.
"I don't regret playing him. But, okay, we know we have a tough programme and we don't have a big squad to resolve that kind of problem with injuries.
"Schneiderlin has a little bit the same as he had when he came back from the French national team. It is an adductor problem in his right leg and he will be out for three or four weeks, like Toby Alderweireld, but, okay, we have a lot of young players."
Those three injuries will seriously test Saints in the coming weeks, starting at Newcastle on Saturday - a Premier League match followed swiftly by the FA Cup clash with Crystal Palace.
Shane Long's first-half goal secured their place in the fourth round, with Koeman satisfied by his side's display against Championship promotion chasers Ipswich.
It was a solid display from Saints that Ipswich counterpart Mick McCarthy could appreciate, even though that organisation and Long's first-half goal made it a "damp squib" of a cup replay.
"Of course it is disappointing for us all," he said. "Somebody said to me after (the home loss to Derby) Saturday 'oh, I am really disappointed' - well, we all are," the Town boss said. "We did not want that game to be like that. We wanted it to be a rip-roaring cup tie. They didn't allow it to happen.
"We should give a bit of credit to them. It is not always us that is to blame - we have tried our hardest, as we always do, but they had a damn good side.
"I watched them beat Arsenal, I watched them beat Manchester United, you know, so it is no great shame on us that we have lost to Southampton. The pity is that we didn't have the exciting cup tie we were all hoping for."