Updated project metadata. The mechanisms by which mosquitoes survive the desiccating conditions of the dry season in West African savannahs and are able to readily transmit malaria as soon as the rains start remain largely unknown. Thus, we examined the degree to which the physiology of 1 h- and 24 h-old female An. gambiae M and S is altered at the onset of the dry season (“ods”) by examining their metabolic fingerprints and protein expression, which were compared to those of females exposed to the rainy season (“rs”) conditions. Three amino acids (phenylalanine, tyrosine and valine) that play a pivotal role in cuticle hardness were significantly decreased from the 1 h- to 24 h-old females, regardless of the experimental conditions. These amino acids were present in higher amounts in 1 h-old female An. gambiae M reared under “ods”; such a seasonal difference was not reported in the female S molecular form. Together with the increased expression of cuticular proteins 70 and 117(spots 67 and 65, respectively), our data suggest that the cuticle thickness, rigidity and permeability were adjusted at the onset of the dry season. Evident signs of energetic metabolism adjustments were found in both of the molecular forms at the onset of the dry season. Moreover, 1 h-old females of An. gambiae S were characterised by elevated amounts of glycogen phosphorylase, isocitrate dehydrogenase and citrate synthase, suggesting an increase of their metabolic activity at the onset of the dry season. This study presents novel insights into drought resistance in the mosquitoes of utmost medical importance.