Abstract Like many marine species around the globe, several stocks of Atlantic cod (Gadus morhua) live in increasingly hypoxic waters. In the Gulf of Saint Lawrence (GSL) in Canada, the deep channels traversing the semi-enclosed sea exhibit year-round hypoxia, identified as one of the limiting factor for the recovery of GSL cod in its northern part. While many individuals in the northern GSL are known to venture in deeper, warmer, and more hypoxic waters of the Gulf channels, those in the southern GSL live in a shallower, colder, and more oxygenated environment. In this study, we use the modeling framework of the Dynamic Energy Budget (DEB) theory to disentangle the effects of hypoxia, temperature and food on the life-history traits of these two populations of cod in the GSL. Following recent advances by Thomas et al. (2018, this issue) on the mechanisms for the effects of hypoxia within the context of DEB theory, we implemented a correction of ingestion depending on dissolved oxygen (DO) saturation. We successfully developed and validated a set of parameters for a GSL Atlantic cod DEB model. Using simulations of historical growth trajectories from 1990 until 2004 estimated from data collected through fisheries research surveys, we found that temperature explained about half (48%) of the difference in length and 59% of the difference in mass between the two populations. The remaining proportion was attributed to exposure to hypoxia and food input. We also used our model to explore scenarios of duration, frequency, and intensity of hypoxia on cod's life-history traits, which showed that decreasing DO linearly reduces growth and reproduction while young cod seem to avoid impairing conditions resulting in limiting effects on developmental stages.