The GLP1R and GIPR are key targets for the treatment of obesity and type 2 diabetes. Despite this, pre-clinical rodent models of obesity favour the use of male mice and the roles of GLP-1R and GIPR in female mice is not well studied. We aimed to characterise any sexual differences in glycaemic control and energy metabolism under normal and diet-induced obesity (DIO) conditions in wild type mice and mice lacking either the GLP-1R or GIPR. Male and female C57Bl/6N (C57), GIPRKO and GLP-1RKO mice were fed a chow or high fat diet (HFD) for 12-weeks before undergoing glucose and insulin tolerance tests, whole-body energy metabolism analysis and brown adipose tissue (BAT) function, assessed by measuring the effect of a b3-adrenoceptor (b3-AR) agonist, CL3162463 1mg/kg ip, on oxygen (VO2) consumption. Body weight and food intake were recorded weekly during the diet. Sex affected BAT function in all strains, where males had increased average VO2 consumption after CL316243 administration whilst females showed no change. Sex also affected insulin tolerance in C57 HFD mice, where males had greater insulin intolerance compared to females. However, the most striking differences occurred between GLP-1RKO HFD mice, where males were more glucose and insulin intolerant, had greater total food intake and had higher average energy expenditure compared to females. Our results indicate that sex has a role in GLP-1R and GIPR function, highlighting the importance of assessing the responsiveness of both male and female animals in the development of novel GLP-1R and GIPR agonists, and highlighting potential differences that may arise in humans using these agonists.