Heat and discomfort indices are applied to the multimodel ensemble mean of COordinated Regional climate Downscaling EXperiment-Africa regional climate model projections to investigate future changes in heat stress and the proportion of human population at risk under 1.5°C and 2°C global warming scenarios over West Africa. The results show that heat stress of category Extreme Caution is projected to extend spatially (up to 25%) over most of the Gulf of Guinea, Sahel, and Sahara desert areas, with different regional coverage during the various seasons. Similarly, the projected seasonal proportion of human population at discomfort substantially increases to more than 50% over most of the region. In particular, in June-August over the Sahel and the western Sahara desert, new areas (15% of West Africa) where most of the population is at risk emerge. This indicates that from 50% to almost everyone over most of the Sahel countries and part of the western Sahara desert is at risk of possible heat cramp, heat exhaustion, and heat stroke in future climate scenarios. These conditions become more frequent and are accompanied by the emergence of days with dangerous heat stress category during which everyone feels discomfort and is vulnerable to a likely heat cramp and heat exhaustion. In general, all the above features are more extended and more frequent in the 2°C than in the 1.5°C scenario. Protective measures are thus required for outdoor workers, occupational settings in hot environments, and people engaged in strenuous activities.