Strepsesquitriol, a new caged sesquiterpene, was isolated from Streptomyces sp. SCSIO 10355. Its absolute structure was established as (1R,2R,4S,5S,8S,10S)-4,9,9,10-tetramethyl-2,5,10-trihydroxytricyclo[6.2.1.0(1,5)]undecane by NMR analysis and a theoretical optical rotation derived from quantum-chemical calculations. It showed moderate inhibitory activity against lipopolysaccharide-induced TNFα production in RAW264.7 macrophages.