Four new steroids with an acetoxy linked at the end of the side chain, echrebsteroids A-D (1-4) were obtained from the South China Sea gorgonian Echinogorgia rebekka. The absolute configurations of 1-3 were determined using the modified Mosher's method on the hydrolysis products. The isolation of the pair of epimers (2 and 3) represents the first reported separation of C-25 epimers of 26-acetoxy steroids. The (25R)-epimer (3) exhibited promising antiviral activity against respiratory syncytial virus with an IC50 value of 0.19 μM and a comparatively higher therapeutic ratio (TC50/IC50 = 128).