Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease globally. MASLD is a multisystem disease where metabolic dysfunction plays a key role in the development of MASLD and its most relevant liver-related morbidities and extrahepatic complications, such as cardiovascular disease, chronic kidney disease and certain types of extrahepatic cancers. Among the least examined MASLD-related extrahepatic complications, an ever-increasing number of observational studies have reported a positive association between MASLD and the risk of serious bacterial infections (SBI) requiring hospital admission. This risk remained significant in those studies where statistical analysis was adjusted for age, sex, ethnicity, obesity, type 2 diabetes and other common comorbidities. Notably, the incidence rates of SBI were further increased with more advanced MASLD, especially in patients with MASLD-related cirrhosis, and were also observed for some acute viral infections, including SARS-CoV-2 infection, leading to severe COVID-19. In this narrative review article, we provide an overview of the literature on (a) the recent epidemiological data linking MASLD to the risk of serious bacterial and non-bacterial infections requiring hospital admission, (b) the putative underlying mechanisms through which MASLD may increase the susceptibility to serious infections, both directly and through the immune dysfunction associated with cirrhosis and portal hypertension, and (c) the practical and clinical implications of the increased risk of serious bacterial and non-bacterial infections in the growing global population with MASLD.