Weight loss is a hallmark of many infections, including those caused by bacteria, fungi and parasites. This loss is often attributed to infection-induced anorexia and the need to mobilise energy from internal sources to cope with the pathogens. Weight loss during infection results from a significant reduction of muscle and fat mass, two organs that together account for approximately 60% of body mass in the healthy state. While muscle wasting is a well-documented aspect of infection-related weight loss, adipose tissue loss via lipolysis also plays a critical role and can determine disease outcomes. This review explores the regulators of adipose tissue depletion via excessive lipolysis during infection, the probable mechanisms, and the potential consequences for host survival and pathogen fitness.