Sepsis is being recognized as an important complication of extracorporeal membrane oxygenation (ECMO) and its presence is a poor prognostic marker and increases the overall mortality. The survival rate differs in the various types of cannulation techniques. Adult patients with prolonged duration of ECMO constitute the major risk population. Ventilator-associated pneumonia and bloodstream infections form the main sources of sepsis in these patients. It is important to know the most common etiological agents for sepsis in ECMO, which varies partly with the local epidemiology of the hospitals. A high index of suspicion, drawing adequate volumes for blood culture and early and timely administration of appropriate empirical antimicrobials can substantially decrease the morbidity and mortality in this high-risk population. The dosing of antimicrobials is influenced by the pharmacological variations on ECMO machine and is an important consideration. Infection control practices are of paramount importance and need to be followed meticulously to prevent sepsis in ECMO.© Indian Association of Cardiovascular-Thoracic Surgeons 2020.