Many reports showed a dramatic decrease in the levels of physical activity during the current pandemic of SARS-COV-2. This has substantial immunometabolic implications, especially in those at risk or with metabolic diseases including individuals with obesity and Type 2 diabetes. Here we discuss the route from physical inactivity to immnometabolic aberrancies; focusing on how insulin resistance could represent an adaptive mechanism to the low physical activity levels and/or high energy intake and on how such an adaptive mechanism could derail to be a pathognomonic feature of metabolic diseases creating a vicious circle of immune and metabolic aberrancies. We provide a theoretical framework to the severe immunopathology of COVID-19 in patients with metabolic diseases. We finally discuss the idea of exercise as a potential adjuvant against COVID-19 and emphasize how even interrupting prolonged periods of sitting with short time breaks of very light activity could be a feasible strategy to limit the deleterious effects of sedentary behavior.