The centre-back, who joined from French side Lyon in the summer, was stretchered off in the south-coast side's 2-2 draw with Sunderland and is now set for a spell on the sidelines
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"Croatian defender Dejan Lovren will be out for several weeks due to an ankle injury sustained in the match with Sunderland," read a statement on the Croatian FA's website on Tuesday.
"(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 and netting twice in the Premier League.
When contacted, Southampton were unable to confirm the length of Lovren's absence.