Introduction: Kalanchoe pinnata extracts have been shown to possess beneficial cardiovascular effects, analgesic and myorelaxant activities. This study aimed at evaluating the haematological and anti-fatigue effects of its aqueous extract. Materials and methods: This was an in vivo pharmacological experiment, carried out in the Laboratory of Zoology, University of Buea, from January to May 2018. A total of 48 mice were subjected to a 90mins/day-free endurance swimming test for 14 days. Two groups of mice received distilled water and 12% NaCl solution, respectively. Five groups received the plant extract (25, 50, 100 and 200 mg/kg/day) and 200mg/kg/day+NaCl. One positive control group received 5% Vitamin C (1.97mg/kg/day). All administrations were by gavage. Maximum swimming time, glycaemia, lactatemia, uremia, triglyceridemia, haematological indices, tissue glutathion peroxidase, malondialdehyde, glucose and creatine kinase-MB in the heart or gastrocnemius muscle were measured. Results: K. pinnata (50 and 100mg/kg/day) induced a non-significant increase of the swimming duration, compared to neutral control. However, the 12%NaCl group recorded a significant (P<0.05) increase. In the blood, NaCl induced a decrease of platelets that was significantly reverted by the extract in the 200mg/kg+NaCl group. The extract prevented the increase of the level of CK-MB in NaCl group and decreased the serum triglycerides, glucose, urea nitrogen and Lactate levels. In the tissues, MDA and CK-MB levels significantly increased (P<0.001) in the negative control. These increases were significantly (P<0.001) prevented by K. pinnata (200mg/kg/day). Conclusions: Significant biochemical variations support the hypothesis that K. pinnata could be used to delay exercise induced fatigue.