Context: Lepidium meyenii Walp. (Brassicaceae), most commonly known as "maca", has been used as a food or folk medicine to improve vitality in Peru. Previous research demonstrated that lipid-soluble extract from maca improved swimming endurance capacity. Macamides are considered the typical lipid-soluble markers for maca and proved to have several pharmacological properties, such as improving sexual performance and neuroprotective activies.Objective: The present study investigates the effects of macamides on endurance capacity and anti-fatigue property in prolonged swimming mice.Materials and methods: The Balb/c mice were divided into seven groups: a control group, low-dose groups of N-benzyllinoleamide, N-benzyloleamide, and N-benzylpalmitamide, high-dose groups of these macamides. The macamides groups received the commercial products (12 and 40 mg/kg, ig), while the control group received vehicle for 21 d. On the 14th day, the mice were given the weight-loaded swimming test. On the 21st day, the mice were sacrificed immediately after 90 min swimming, and some biochemical parameters were measured.Results and discussion: Compared with the control group, exhaustive swimming time was significantly prolonged in high-dose group of N-benzyloleamide (p < 0.05); the levels of lactic acid (LD), blood ammonia (BA), and lactate dehydrogenase (LDH) were significantly decreased (p < 0.05), whereas the levels of liver glycogen (LG) and non-esterified fatty acid (NEFA) were significantly increased (p < 0.05) in high-dose group of N-benzyloleamide. The malondialdehyde (MDA) contents in the brain, muscle, and liver were significantly decreased (p < 0.05), whereas superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities in the brain, muscle, and liver were significantly increased in high-dose group of N-benzyloleamide (p < 0.05).Conclusion: The results indicate that N-benzyloleamide has pharmaceutical property against exercise-induced fatigue, and this effect can be explained by the modulated energy metabolism and improved antioxidant status. © 2015 Taylor & Francis.