Sida linifolia L., a common weed found in dry forest areas in West Africa and other parts of the world, is associated with several folkloric applications in Africa, including its use in assuaging painful whitlows and in malaria management; however, scanty or no scientific study has validated its bioactivities. Herein, we investigated the anti-nociceptive and anti-inflammatory mechanisms of ethanolic (ELFSL) and ethyl acetate (EALFSL) fractions of Sida linifolia leaves. The in vivo anti-inflammatory activities were evaluated by edema induction with an intraperitoneal injection of freshly prepared carrageenan (0.1 ml of 0.01 g/ml) and 0.1 ml of undiluted fresh egg albumin into mice's hind paw, while hind paw licking and writhing were induced in mice using formalin (i.p.) (0.02 ml of 1 % v/v) and 0.6 % (v/v) (10 ml/kg bw) (i.p.) acetic acid, respectively, to assay for the anti-nociceptive potentials. Varying amounts of flavonoids, tannins, and other phenols, terpenoids, saponins, steroids, and alkaloids were detected in the fractions. The LD₅₀ study showed no toxicity up to 5000 mg/kg body weight (per oral) EALFSL and ELFSL. Interestingly, oral administration of various concentrations (200, 400 and 600 mg/kg bw) of the fractions significantly (P < 0.05) inhibited all phases of edemogenesis, mice's hind licking, and writhing compared with control and were comparable with 100 mg/kg bw (p.o.) aspirin. However, ELFSL showed significantly (P > 0.05) better anti-nociceptive and anti-inflammatory activities than EAFSL. These suggest that leaf fractions of Sida linifolia possess anti-inflammatory and anti-nociceptive potentials, possibly mediated by peripheral and central mechanisms.