Defender Branislav Ivanovic and midfielder Frank Lampard both picked up knocks in Sunday's 2-1 win over Liverpool, while David Luiz is suspended for the trip to St Mary's Stadium
The west Londoners' 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 field with injuries, while David Luiz is also out due to suspension after picking up his fifth yellow card of the season.
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"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 Stadium.
"(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."
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 Chelsea performing 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," Mourinho added.
"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."