Background: The present study evaluated levels of polymerization of deoxygenated sickle hemoglobin molecules (poly-dHbS-M) in the presence of fractionated leaf extracts of Anacardium occidentale Linn., Psidium guajava Linn., and Terminalia catappa Linn in vitro as well as identified, quantified, and characterized the phytocomponents from fractionated leaf extracts that exhibited comparatively high potency to impede poly-dHbS-M. Non-hemolyzed sickle erythrocytes were premixed with 40, 60, and 80 mg/100 mL of each of the separate fractionated leaf extracts of A. occidentale, P. guajava, and T. catappa in phosphate-buffered saline (PBS; pH = 7.4), osmotically equivalent to 9.0 g/ L NaCl. Poly-dHbS-M was induced by adding 2.0 g/100 mL Na 2 S 2 O 5 to the erythrocyte suspension. The absorbance of the erythrocyte suspension was measured at regular intervals of 30 s for 180 s. Identification, quantification, and characterization of phytocomponents from fractionated leaf extracts were carried out using GC-MS, FT-IR, and UVvisible systems protocols. Results: The level of poly-dHbS-M of the control sample was significantly higher (p < 0.05) than those of the samples containing 40, 60, and 80 mg/100 mL ethylacetate extracts of A. occidentale at t < 60 s. The relative cumulative polymerization index (RCPI%) of dHbS-M in the presence of fractionated leaf extract of A. occidentale varied within a wide range of 3.8-59.4%. A. occidentale (petroleum ether and ethylacetate extracts), P. guajava (nhexane, chloroform, and ethylacetate extracts), and T. catappa (ethylacetate extract) exhibited comparatively high potency to inhibit poly-dHbS-M. Conclusion: The fractionated leaf extracts of A. occidentale, P. guajava, and T. catappa exhibited differential capacities to impede poly-dHbS-M. The combinations of aliphatic hydrocarbons, methylated esters, methylated fatty acids, aliphatic alcohols, D-erythro-sphinganine, aromatic derivatives, cycloalkanes, phthalates, isothiocyanates, aminated sugars, cyclo-alcohols, and nitro-compounds impeded poly-dHbS-M.