The leaves extracts of Telfairia occidentalis (Hook f) was studied as a potential antisickling agent. By solvent extraction, ethanol crude extract of leaves of Telfairia Occidentalis were partitioned to obtain their active fractions. In-vitro antisickling activity was determined using freshly prepared 2% sodium metabisulphite (negative control) and extracts of the plant (positive control) against haemoglobin SS red blood cell (HbSS). Activity- guided fractionation was used to target antisickling constituents of n-hexane fraction. The active principle in the fraction was isolated and further purified using vacuum liquid chromatography and sephadex LH-20 column respectively. The purified samples were analyzed by HPLC-UV detector and the identified compounds were chlorogenic acid, 4-hydroxybenzoic acid, beta-carotene, gallic acid, caffeic acid, catechin, protocatechuic acid, beta-sitosterol, P-coumaric acid, lutein, sinapic acid, kaempferol, rutin, zeaxanthine, ferulic acid, vanillic acid and inositol. Hydroxybenzoic acid is a known antisickling drug. In this study a derivative (4-hydroxy benzoic acid) was detected in both isolated fraction of the leaves of T. occidentalis thus supporting among other constituents for the antisickling results.