As well as the suspension of DeAndre Yedlin, following his straight red card in United's home defeat to Wolves, Benitez will also be without Federico Fernández, Jonjo Shelvey and Karl Darlow.
Fernández, who was taken off at half-time against Wolves last week, has been unable to recover from his injury in time to face the Terriers.
However, despite losing two defenders, Benítez was keen to point out the excellent progress made by Florian Lejeune, who featured for United's under-23s on Monday night after recovering from an anterior cruciate ligament injury sustained in pre-season.
"The problem we have is that Yedlin is suspended," Benitez said. "Fede Fernandez has a knock on his calf and, although he is still progressing, he is not available for the game.
"Darlow has a problem but hopefully he will be fully fit and back next week. Shelvey is another one that we have to assess in around ten days so we'll have to see how he is doing and decide how long it will take.
"Florian is getting closer to playing but he will not play against Huddersfield. For Lejeune, it is great news because, if you think about his cruciate ligament injury, normally it takes six to nine months to recover. In four months, he is already playing so I think it is very good news for the team."
With only three points separating United and Huddersfield, who occupy the final space in the relegation zone on ten points, the Spaniard insisted that the Magpies are fully prepared for the task ahead of them.
Benítez added: "The squad know that every game is really important for us and especially these kind of games where you are both so close in the table.
"Sometimes, you talk about six point games rather than three point ones.
"The players know this is one of those and the group are quite good in terms of their approach to matches. We need them to gain confidence to allow them to do things in the correct way."