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We assessed the impact of the first wave of COVID-19 pandemic on non-COVID hospital admissions, non-COVID mortality, factors associated with non-COVID mortality, and changes in the profile of non- COVID patients admitted to hospital. We used the Spanish Minimum Basic Data Set with diagnosis grouped according to the Diagnostic Related Groups. A total of 10,594 patients (3% COVID-19; 97% non-COVID) hospitalised during the first wave in 2020 (27-February/07-June) were compared with those hospitalised within the same dates of 2017–2019 (average annual admissions: 14,037). We found a decrease in non-COVID medical (22%) and surgical (33%) hospitalisations and a 25.7% increase in hospital mortality among non-COVID patients during the first pandemic wave compared to prepandemic years. During the officially declared sub-period of excess mortality in the area (17-March/20- April, in-hospital non-COVID mortality was even higher (58.7% higher than the pre-pandemic years). Non-COVID patients hospitalised during the first pandemic wave (compared to pre-pandemic years) were older, more frequently men, with longer hospital stay and increased disease severity. Hospitalisation during the first pandemic wave in 2020, compared to hospitalisation during the prepandemic years, was an independent risk factor for non-COVID mortality (HR 1.30, 95% CI 1.07–1.57, p = 0.008), reflecting the negative impact of the pandemic on hospitalised patients.