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Background: The benefit of antibiotics in leptospirosis is limited when treatment is started four days after symptoms appear, and new adjuvant therapeutic options are urgently needed., Methods: Hamsters (Mesocricetus auratus) were infected by Leptospira interrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2)., Results: Experiment 1: all hamsters from the groups AMP and AMP-TAL survived (n=8), while all hamsters from groups NONE (n=6) and TAL (n=8) died. The AMP and the AMP-TAL groups showed no renal or liver pathology and absent or very low leptospiral burden in target organs. Experiment 2: lethal outcome was observed in 6/6 hamsters in the NONE group, 8/8 in the TAL group, and 6/8 in both the AMP and AMP-TAL groups. Thalidomide showed no survival benefit when compared to hamsters treated with ampicillin alone. The TAL, AMP and AMP-TAL groups had very low tissue leptospiral counts., Conclusion: Thalidomide had minimal impact on survival in the late treatment of leptospirosis hamster model.