The objective was to investigate the impact of COVID-19 vaccination on anxiety, depression, stress perception, and psychiatric symptoms in patients with schizophrenia, and to explore severity of psychiatric symptoms is associated with vaccine hesitancy in individuals with schizophrenia. Mental health symptoms were evaluated in 273 hospitalized schizophrenia patients who received COVID-19 vaccination, and in 80 patients who refused vaccination, both before and after immunization. The study assessed the effects of vaccination on psychiatric symptoms and the potential association between vaccination behavior and psychological distress. Our findings suggest that COVID-19 vaccination is associated with a small worsening of schizophrenia symptoms in older inpatients. Moreover, vaccination behavior may increase anxiety, depression, and stress perception in hospitalized schizophrenia patients, which has implications for the mental health care team working in the context of the pandemic. The study highlights the importance of monitoring the mental health status of patients with schizophrenia during the COVID-19 pandemic, particularly in relation to vaccination behavior. Further research is needed to better understand the mechanisms underlying the observed effects of COVID-19 vaccination on psychiatric symptoms in patients with schizophrenia.