Normobaric hypoxic conditioning (HC) denotes exposure to hypoxia at rest (passive) or combined with exercise (active). HC has been applied acutely (single exposure) and chronically (repeated exposure) to obese populations for managing/increasing cardio-metabolic health and weight loss. Cardio-metabolic health and weight loss responses of obese populations in response to passive and active HC are unclear. A systematic search for articles published between 2000-2017 was carried out. Studies investigating the effects of HC for improving cardio-metabolic health and weight loss of obese populations were included. Studies investigated passive (n = 7; 5 animal, 2 humans), active (n = 4; all humans) and a combination of (n = 4; 3 animal, 1 human) HC to an inspired oxygen fraction between 4.8-15.0%, during a single session and daily sessions per week, lasting between 5 days and 8 months. Passive HC could reduce insulin concentrations (-37-22%) and increase energy expenditure (+12-16). Active HC may reduce body weight (-4-2%) and blood pressure (-8-3%). Inconclusive findings exist in determining the impact of acute and chronic HC on markers of triglycerides, cholesterol levels and fitness capacity. Studies that included animal models involved exposure to severe levels of hypoxia (inspired oxygen fraction of 5.0%; simulated altitude >10,000 m) that are not suitable for human populations. HC demonstrated positive findings in relation to insulin and energy expenditure, and body weight and blood pressure, for improving the cardio-metabolic health and body weight management of obese populations. Responses of plasma biomarkers to passive and active HC in humans is warranted.