The African malaria mosquitoes Anopheles gambiae and Anopheles coluzzii range over forests and arid areas, where they withstand dry spells and months-long dry seasons, suggesting variation in their desiccation tolerance. We subjected a laboratory colony (G3) and wild Sahelian mosquitoes during the rainy and dry seasons to desiccation assays. The thoracic spiracles and amount and composition of cuticular hydrocarbons (CHCs) of individual mosquitoes were measured to determine the effects of these traits on desiccation tolerance. The relative humidity of the assay, body water available, rate of water loss and water content at death accounted for 88% of the variation in desiccation tolerance. Spiracle size did not affect the rate of water loss or desiccation tolerance of the colony mosquitoes, as was the case for the total CHCs. However, six CHCs accounted for 71% of the variation in desiccation tolerance and three accounted for 72% of the variation in the rate of water loss. Wild A. coluzzii exhibited elevated desiccation tolerance during the dry season. During that time, relative thorax and spiracle sizes were smaller than during the rainy season. A smaller spiracle size appeared to increase A. coluzzii's desiccation tolerance, but was not statistically significant. Seasonal changes in CHC composition were detected in Sahelian A. coluzzii Stepwise regression models suggested the effect of particular CHCs on desiccation tolerance. In conclusion, the combination of particular CHCs along with the total amount of CHCs is a primary mechanism conferring desiccation tolerance in A. coluzzii, while variation in spiracle size might be a secondary mechanism.