Caretaker manager John McMahon says Tranmere have the scope to go back into the loan market for new signings after the two Matts were recalled by Everton.
Winger Matthew Kennedy, 19 and defender Matthew Pennington, also 19, spent close to two months at Prenton Park on youth loans, which meant they could be recalled by their parent club at any time.
The pair had been first-team regulars, with Pennington making nine appearances and scoring one goal and Kennedy playing eight games.
McMahon said: "It is a blow because they are two very good lads, two very good players and they will be missed. It is up to us now to fill voids, whether it be in-house or getting new players in. That is up to us as a club.
"We still have good players here and we can have a look at the situation. We will adjust."
McMahon says Tranmere have "room for manoeuvre" in the budget now that they have only two loan players, defender Stephen Arthurworrey (from Fulham) and striker Jake Cassidy (from Wolves) on the books.
Rovers also have two of their own players out on loan to other clubs in striker Jean-Louis Akpa Akpro (with Rochdale) and Akpo Sodje (with Macclesfield).
Mahon said he has spoken to Danny Holmes, the right back who lost his first-team spot when Pennington arrived in January. "I have told Danny Holmes what would be expected of him, it is potentially an opportunity for him," McMahon said.
"Whether we decide to put Danny in or choose to bring in someone else, is a decision we need to make."
Andy Robinson and Abdulai Baggie look to have most to gain from the departure of wide man Kennedy. McMahon says he will be looking at players' performances in a reserve game against Morecambe at Cammell Laird FC this afternoon (1pm).
Mahon said he wanted to say they thank you to Kennedy, Pennington and Everton manager Roberto Martinez. He said: "The two players have been fantastic around the place and it is a credit to the way they have been brought up and developed at Everton. They are really good types.
"We have to say a big thank you to Roberto Martinez for allowing them out to us."
Tranmere posted a 3-1 win over Coventry City in McMahon's first game in charge since taking over responsibility for team affairs from the suspended Ronnie Moore at the start of last week.
The success, only Rovers' fourth victory at home in the League One campaign, edged them another point further away from the relegation places.
McMahon said: "I was pleased for the players because they have worked hard and it was also important for the spectators. They pay good money to come and support the club and they want to be entertained.
"I was pleased with them more than me personally. I'm just doing the job.
"I think the performance showed me there is a lot of character among the players. They stuck together and put in a good performance.
"In terms of confidence, being bright, energetic and looking as if we can cause problems for the opposing team, I think they did all the right things."
Tranmere are hopeful the four players who suffered minor knocks and strains during the Coventry game will be fit and available for the League One encounter with Oldham Athletic at Prenton Park this weekend.
McMahon says assessments are being made on the condition of striker Jake Cassidy, who has stud marks on his chest, Ryan Lowe (hip) Steve Jennings (knee) and Liam Ridehalgh (dead leg).
"Fingers crossed they will all be fine for the weekend," McMahon said.