The Croatia international was carried off on a stretcher in the latter stages of Southampton's 2-2 draw at Sunderland on Saturday, with forward Gaston Ramirez taken from the field with a similar issue at the same time.
A statement on the Croatian FA's website on Tuesday read: "Croatian defender Dejan Lovren will be out for several weeks due to an ankle injury sustained in the match with Sunderland.
"(He) will wear a protective boot for walking, and the (absence from the) field will be 3-4 weeks."
Should the Croatian FA's timescale prove accurate, Lovren will miss Southampton's FA Cup fourth-round tie against Yeovil Town, as well as Premier League fixtures with Arsenal, Fulham, Stoke City and Hull City.
Lovren has become an instant fans favourite at St Mary's Stadium since signing from Lyon in the close-season, making 20 appearances thus far.
When contacted by Perform, Southampton were unable to confirm the length of Lovren's absence.
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