It remains unknown to what degree resource prioritization toward SARS-CoV-2 (2019-nCoV) coronavirus (COVID-19) cases had disrupted usual acute care for non-COVID-19 patients, especially in the most vulnerable populations such as patients with schizophrenia. The objective was to establish whether the impact of the COVID-19 pandemic on non-COVID-19 hospital mortality and access to hospital care differed between patients with schizophrenia versus without severe mental disorder. We conducted a nationwide population-based cohort study of all non-COVID-19 acute hospitalizations in the pre-COVID-19 (March 1, 2019 through December 31, 2019) and COVID-19 (March 1, 2020 through December 31, 2020) periods in France. We divided the population into patients with schizophrenia and age/sex-matched patients without severe mental disorder (1:10). Using a difference-in-differences approach, we performed multivariate patient-level logistic regression models (adjusted odds ratio, aOR) with adjustment for complementary health insurance, smoking, alcohol and substance addiction, Charlson comorbidity score, origin of the patient, category of care, intensive care unit (ICU) care, major diagnosis groups and hospital characteristics. A total of 198,186 patients with schizophrenia were matched with 1,981,860 controls. The 90-day hospital mortality in patients with schizophrenia increased significantly more versus controls (aOR = 1.18; p < 0.001). This increased mortality was found for poisoning and injury (aOR = 1.26; p = 0.033), respiratory diseases (aOR = 1.19; p = 0.008) and for both surgery (aOR = 1.26; p = 0.008) and medical care settings (aOR = 1.16; p = 0.001). Significant changes in the case mix were noted with reduced admission in the ICU and for several somatic diseases including cancer, circulatory and digestive diseases and stroke for patients with schizophrenia compared to controls. These results suggest a greater deterioration in access to, effectiveness and safety of non-COVID-19 acute care in patients with schizophrenia compared to patients without severe mental disorders. These findings question hospitals’ resilience pertaining to patient safety and underline the importance of developing specific strategies for vulnerable patients in anticipation of future public health emergencies.