BackgroundThe coronavirus disease 2019 (COVID-19) pandemic and related countermeasures hinder health care access and affect mental wellbeing of non-COVID-19 patients. There is lack of evidence on distress and mental health of patients hospitalized due to other reasons than COVID-19—a vulnerable population group in two ways: First, given their risk for physical diseases, they are at increased risk for severe courses and death related to COVID-19. Second, they may struggle particularly with COVID-19 restrictions due to their dependence on social support. Therefore, we investigated the association of intensity of COVID-19 restrictions with levels of COVID-19-related distress, mental health (depression, anxiety, somatic symptom disorder, and mental quality of life), and perceived social support among Swiss general hospital non-COVID-19 inpatients.MethodsWe analyzed distress of 873 hospital inpatients not admitted for COVID-19, recruited from internal medicine, gynecology, rheumatology, rehabilitation, acute geriatrics, and geriatric rehabilitation wards of three hospitals. We assessed distress due to the COVID-19 pandemic, and four indicators of mental health: depressive and anxiety symptom severity, psychological distress associated with somatic symptoms, and the mental component of health-related quality of life; additionally, we assessed social support. The data collection period was divided into modest (June 9 to October 18, 2020) and strong (October 19, 2020, to April 17, 2021) COVID-19 restrictions, based on the Oxford Stringency Index for Switzerland.ResultsAn additional 13% (95%-Confidence Interval 4–21%) and 9% (1–16%) of hospital inpatients reported distress related to leisure time and loneliness, respectively, during strong COVID-19 restrictions compared to times of modest restrictions. There was no evidence for changes in mental health or social support.ConclusionsFocusing on the vulnerable population of general hospital inpatients not admitted for COVID-19, our results suggest that tightening of COVID-19 restrictions in October 2020 was associated with increased COVID-19-related distress regarding leisure time and loneliness, with no evidence for a related decrease in mental health. If this association was causal, safe measures to increase social interaction (e.g., virtual encounters and outdoor activities) are highly warranted.Trial registrationwww.ClinicalTrials.gov, identifier: NCT04269005.