Raphael Varane and Jonny Evans are the latest names on the long list of injuries at United as the duo joined fellow centre-backs Lisandro Martinez and Victor Lindelof and left-backs Luke Shaw and Tyrell Malacia on the sidelines.
United, sixth in the league standings with 49 points, next visit Bournemouth on Saturday. United are 11 points behind fourth-placed Tottenham Hotspur with seven games remaining.
"It's very difficult," Ten Hag told reporters on Friday.
"Everyone who has a little bit of knowledge about football, they know it will effect your performance and your results so the back four is always the foundation to get results.
"We didn't have that but still we have to win. We all have to take the responsibility but when you oversee it, then you know it has a negative impact."
The Dutchman said Harry Maguire, who was linked with a move away from the club in the close season last year, has been an important figure in the team.
"We were always happy with Harry, but he wants to play," Ten Hag said.
"He's a great leader, very good defender, very comfortable on the ball. When I count all of those abilities when we have our (injury) problems in our defensive line, he is even more important to lead that line, to make us play from the back.
"We are very pleased he's there and we need him to get our results and achieve our targets."
To make matters worse, forward Marcus Rashford and midfielder Scott McTominay are a doubt for the clash against Bournemouth, who are 12th. The pair are set to be assessed before the game.
"Scott, I don't think so. We have training, so we have a day, he will push. He's so keen to be a part of it, but there's questions," Ten Hag said.
"Rashy trained yesterday, and we'll see how he recovers from it today. There's another training today and then we will make the decision."
United were stunned by Andoni Iraola's Bournemouth 3-0 in the reverse fixture in December.
