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Background: Regular moderate intensity physical activity and lipid lowering effects of Nigella sativa (N. sativa) supplementation may be appropriate management for sedentary overweight females. Therefore, the aim of the present study was to examine the effects of long-term N. sativa supplementation and aerobic training on lipid profile and maximal oxygen consumption (VO 2 max) in sedentary overweight females. Methods: In this randomized, double-blind, controlled trial, which was conducted in Kerman city (Iran), 20 sedentary overweight females were divided into two groups and assigned to N. sativa supplementation (N. sativa capsules) or a placebo for the 8 weeks, both groups participated in an aerobic training program (3 times/week). Each N. sativa capsule contained 500 ΁ 10 mg N. sativa crushed seeds and subjects had to take 2 g N. sativa per day for 8 weeks. Blood lipids and VO 2 max were determined at baseline and at the end of 8 weeks. Results: N. sativa supplementation lowered total cholesterol (TC) (P < 0.01), triglyceride (P < 0.001), low-density lipoprotein (LDL) (P < 0.001) and body mass index (P < 0.01) and increased high density lipoprotein (HDL) and VO 2 max (P < 0.01). Aerobic training program lowered TC (P < 0.001) and LDL (P < 0.01) and increased VO 2 max (P < 0.01). Furthermore, we observed a significant effect of aerobic training program and N. sativa supplementation lowered LDL and HDL (P < 0.05). Conclusions: The present study demonstrates that 8-week aerobic training plus N. sativa supplementation have a synergistic effect in improve profile lipid parameters.