In the onset of COVID-19 era, the nutritional approach might be managed in two different strategies, considering the disease status. In a severe phase of COVID-19 in a patient with obesity, immunonutrition would be fundamental to support the immune response and protein synthesis, and, at the same time, to reduce inflammation caused by the pathological condition. The organism fights both the acute inflammatory state triggered by COVID-19 and, in addition, the latent chronic inflammation due to the obesity condition. This latter is employed in the case of malnourished surgical patients, where immunonutrition significantly reduced the risk of acquired infections, wound complications, and length of stay at the hospital. In this context, immunomodulating diets (IMDs) have been demonstrated to improve immune system response and modulate inflammation cascade [60]. Furthermore, the nutritional approach should be firstly preventive to reduce the large number of complications linked to obesity condition; and, secondly, could be predictive to act on the etiopathogenesis of SARS-CoV-2 disease.