Both missed training on Thursday and were set to be assessed on Friday ahead of the visit to St. Mary’s, where the Blues are looking to bounce back after consecutive heavy defeats to Brentford and Real Madrid.
Ziyech and Lukaku were both introduced from the bench during the loss to Real Madrid at Stamford Bridge on Wednesday night.
Belgian striker Lukaku is suffering with pain in his achillies while Callum Hudson-Odoi is facing a longer spell on the sidelines due to a back issue.
“Hudson-Odoi is still out, and we are a bit in doubt with Romelu Lukaku and Hakim Ziyech,” Tuchel said on Friday.
“Romelu has Achilles pain, as well, just pain, nothing major. They were not in training yesterday due to little problems.
“We hope to have them in training but need a test and confirmation from training.”
Predicted Chelsea XI: Mendy; Chalobah, Rudiger, Christensen; Azpilicutea, Kovacic, Jorginho, Alonso; Mount, Pulisic, Havertz.