While women’s participation in leisure physical activities and competitive sports has progressively increased over the last century, many studies continue to exclude women, to overlook woman-specific features, or to extrapolate data obtained in men to women. In recent decades, several research groups have stressed this weakness and called for a better consideration of women and of their hormonal specificities (Elliott-sale et al. 2021). Specifically, many adult women of childbearing age use hormonal agents that support menstrual regularity and provide birth control, with oral contraceptives (OC) being one of the most popular form. Due to their specific nature and concentrations, synthetic ovarian hormones contained in OC could influence physiological responses during exercise. Substrate metabolism during endurance exercise is a key factor of health management but also of sport performance. Carbohydrates and fat are the two major fuels used by muscles for energy production during endurance exercise, and it is acknowledged that substrate partitioning depends on several inter- and intra-individual factors, including exercise intensity and duration, body composition, training and nutritional status, physical activity level and sex. In addition, due to their specific characteristics, the exogeneous hormones contained in OC are likely to influence substrate metabolism during exercise in women. By analysing the available literature, we will try here to discuss the effect of OC use on substrate metabolism during endurance exercise. Several studies conducted among women using different types of OC showed that substrate oxidation during moderate prolonged exercise was similar to what is observed in non-OC users (Bonen et al. 1991; Casazza et al. 2004; Isacco et al. 2012). Interestingly, some studies specifically reported increased lipolysis or decreased glucose flux without any change in substrate oxidation rates during endurance exercise in women using OC (Casazza et al. 2004; Isacco et al. 2012 and 2014). In addition, we previously reported that although OC use increases lipid mobilization, this effect was blunted by the lipolytic activity that occurs during endurance exercise (Isacco et al. 2014). Results on the effect of synthetic ovarian hormones contained in OC on substrate metabolism during endurance exercise remain however unclear to date. While there are important heath and performance implications regarding the use of OC among women, further studies are today needed to better understand this increased lipolytic activity without any substantial (or detectable) effect on substrate use during endurance exercise in OC users.