Context: Costus afer Ker Gawl. (Costaceae) is an ethnomedical plant used as therapy against inflammatory disorders. Objective: The objective of this study was to evaluate the hematological and lipid profile analysis of hexane fraction of C. afer leaves (CAHLF) in arthritic rats. Materials and methods: Male albino rats were randomly distributed into seven groups of six rats each. Rats were induced with arthritis using formaldehyde and Complete Freund's Adjuvant (CFA) for 7 and 21 d, respectively. The animals were administered orally with 50, 100, and 250 mg/kg CAHLF, 10 mg/kg diclofenac and prednisolone, 0.9% NaCl (control), and 0.9% NaCl (normal). At the end of treatment periods, blood samples were withdrawn and subjected to hematological and biochemical analysis using auto-analyzer and spectrophotometric methods. Results: Hematological analysis revealed that in formaldehyde-and CFA-induced arthritic rat models, 250 mg/kg CAHLF-treated groups had significantly reduced (p50.05) hematocrit counts (HC) (30.98 ± 1.59% and 33.55 ± 1.10%), white blood cell counts ( /L). Furthermore, blood analysis showed that CAHLF-treated groups had reduced total cholesterol, low-density lipoprotein cholesterol, and triglycerides while they had an elevated high-density lipoprotein compared with the control group. Discussion and conclusion: Findings from this study indicated that CAHLF could possess immunomodulatory and hypolipidemic properties in arthritic rats. CAHLF could be considered as a source of biopharmaceutical agents in anti-arthritis drug discovery process.