Lejeune suffered an injury to his left knee in Saturday's 1-0 home defeat against Crystal Palace, ruling the centre-back out for the remainder of the season.
After the disappointing blow, Benítez is hopeful Lejeune can bounce back from another unfortunate setback, with the 27-year-old suffering an anterior cruciate ligament injury in pre-season which kept the Frenchman out until December.
Benítez said: "We have Lejeune injured, Longstaff too, and the rest of the players are available. Florian did very well because in four months he was fine when normally it takes six or seven months (to recover).
"When he was not playing, we were not doing so well. When he came back, he helped us pick some good results, not just because of him, but because he is comfortable on the ball.
"Now, we have to manage again and hopefully the other players can do well. We can change and play with four or five at the back. We can manage, but it is never good news to lose such an important player. He was really unlucky that he has suffered a similar injury but on the opposite knee. We hope he has a good operation and comes back soon."
Leicester - who earned a 2-0 win at St. James' Park in September - are enduring a purple patch under new manager Brendan Rodgers, with the Foxes situated in seventh spot following a four-game winning streak.
After United's narrow 1-0 defeat to Crystal Palace on Saturday, Benítez remains optimistic that the Magpies can claim a positive result to move closer towards Premier League safety.
Benítez added: “(Leicester) are a very good team. They have won some games in a row and they are playing with more confidence now, and it will be tough for us. We have to do our job on Friday and win the game if we can and then try to finish as high as possible. It’s one game at a time.
"I had confidence that we could do it (against Crystal Palace) and I think we did enough to get at least one point or even three.
"It didn't happen so we have five games and we have to think of every one like a final, as we have said many times. We must approach every game with confidence, calmness, and the belief that we can do it.
"I was quite disappointed because we created enough chances to win the game and we lost in a way that you never want to lose. It was an important game where we could have been safe which was more disappointing. We had a bad day but, after that, we have to be ready for the next game."
