Here we demonstrate that loss-of-function of SCD1 in adult female A. coluzzii mosquitoes, the main vector of human malaria in West and Central sub-Saharan Africa, leads, upon blood feeding, to a highly skewed SFA:UFA ratio, loss of cell membrane integrity, transcriptional and metabolic reprogramming and various other detrimental physiological effects, including an acute auto-inflammatory condition and compromised reproduction. Here, SCD is linked to malaria.