In a nationwide analysis of hospitalizations in the USA between 2006 and 2016 (n = 340,467,049), the risk of death decreased from 2.2% to 1.5% during this period among patients with a diagnosis of systemic lupus erythematosus (SLE; n = 1,903,279). Compared with non-SLE hospitalizations, SLE hospitalizations were more likely to end in death in 2006, but in-hospital survival for SLE hospitalizations improved from 2006 to 2008 and then plateaued, after which mortality was similar between the two groups. Mortality was highest among SLE populations classified as ‘black’, ‘Hispanic’ or ‘Asian/Pacific Islander’.