Stuart Armstrong tested positive for COVID-19 while on international duty with Scotland. As he has had to self-isolate since, the midfielder will miss out on the Chelsea trip.
The Scot will return to training on Friday, but Hasenhuttl believes he will not be in the right physical condition to play.
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Winger Moussa Djenepo will also miss out on any football this weekend.
Hasenhuttl said the Malian picked up a hamstring injury in Saints’ 2-0 victory over West Bromwich Albion a fortnight ago.
These selection issues could leave the door open for Theo Walcott to make his first appearance for Southampton in about 15 years. Though, it’s unclear whether fellow new signing Ibrahima Diallo will feature.
“With all the injuries we have in the number 10 position, with Stuey out and Moussa out, Theo has more chance to play on the weekend,” Hasenhuttl said in his pre-match press conference. “With Ibrahima it’s a bit more difficult.
“He was not here for the whole week – just one session yesterday (Wednesday), so we are just starting work with him, which may take a little bit longer.”