Goals from Ansu Fati and Simon Adingra secured back-to-back wins – and consecutive clean sheets – over Dutch giants Ajax.
It was almost a perfect night but defenders Lewis Dunk, Pervis Estupnian and James Milner suffered concerning-looking injuries.
Milner, the most experienced player in the squad, suffered a knock in the first-half and was unable to continue. The captain, Dunk – who was named in the latest England squad – pulled up with a groin injury before the half-time whistle.
He tried to carry on but did not emerge for the second-half, with Igor taking his place. Estupinan, who was making his return from a long-term muscle injury, had to leave the field just 12 minutes after replacing Mahmoud Dahoud.
Addressing the three injuries post-match, De Zerbi said: "I think they are not so important injuries, I hope.
"But anyway we have to find different solutions in terms of players because it is very tough this season.
"I I knew before the season [it] could be so difficult, so tough and in this moment it is very tough [to] find the first 11.
"But Sunday we have a crucial game for us [against Sheffield United].
"We want to go back to a win, a victory at home with our fans. They have to help us because we are very tired but we need three points and we will be enough to try [to get] the victory on Sunday."