Sepsis is characterised as life-threatening and fast-progressing organ dysfunction caused by a dysregulated host response to infection. Sepsis shares several clinical manifestations with COVID-19, making diagnosis challenging. SARS-CoV-2 co-infection, where an individual may be infected with the virus and one or more additional pathogens concomitantly, leads to both innate and adaptive immune responses, which in some cases of severe disease, can become dysfunctional and cause significant lung and systemic pathology. Philip Perry at Bruker Daltonics GmbH & Co. explains why it is vitally important to rapidly detect co-infection in COVID-19 patients and accurately identify causative pathogens to deliver effective treatment.