The Blues' vital 2-1 win over Liverpool on Sunday came at a cost with defender Branislav Ivanovic and veteran midfielder Frank Lampard both forced off the ground with injuries, while enigmatic utility David Luiz is also out due to suspension after picking up his fifth yellow card of the season.
While the return of Ramires will ease Mourinho's selection headaches, the former Inter and Real Madrid manager admits it is not an ideal situation to be in as they prepare to face one of the surprise packets of the Premier League this season.
"We lost David (Luiz) because of yellow cards, we lost Ivanovic and Lampard with injuries. We've recovered Ramires but we are still in a difficult situation," he said ahead of the game at St Mary's.
"(Southampton are) another team with good players who are influenced by the manager's culture in the way they play and the way they build. And they feel very comfortable at home so it is another very, very difficult match."
Compounding what is already a difficult trip to the south coast is the fact Southampton are near full-strength and despite Mauricio Pochettino's men not enjoying the form they showed early in the season they will be no pushovers, with Mourinho looking forward to the challenge.
"I had a quick look at their team selection and I think that only (Artur) Boruc and (Victor) Wanayama were not in the team - everyone else was," he said.
"So they must be in the maximum of their strength so it's a big game but it is good for us.
"We are in the top four - two points off the leader - so let's enjoy the 31st of (December) in the hotel."
Mourinho also stressed the importance of staying in the top four in what is one of the most congested Premier League tables in recent memory.
Just nine points separate first and eighth and with the Blues tracking far better than they were this time last year, the Portuguese manager is keen to keep his side near the top of the table.
"We are ok. Last year in this moment we were 12 points behind the leader so game over. In this moment we are two points behind so game on! Let's keep going," he said.
"We have to protect the top four because the top four this season will be a big achievement for anyone.
"And if we can protect the top four let's see what we can do and let's see if Manchester City kills everybody or if they stay close to all of us."
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