Psychiatric patients on inpatient care are at high risk of acquiring and transmitting communicable diseases such as SARS-CoV-2 (COVID-19). The authors conducted a retrospective review of the medical records of COVID-positive inpatients at Valleywise Health Medical Center, Arizona, USA from March to June 2020. The authors examined a cohort of COVID-positive inpatients admitted early in the pandemic to assess the ways in which the virus and infection prevention and control (IPC) measures affected patients at a large psychiatric hospital. Data was gathered for demographics, psychiatric diagnoses, COVID-19 symptoms, medical co-morbidities, and length of stay. Initial and revised hospital policies and procedures, and emergent challenges in managing this highly contagious disease in the inpatient psychiatric setting, were examined by review of relevant documents and direct observation by board certified psychiatrists who provided direct care. Significant challenges were encountered in balancing the need for a therapeutic milieu and compliance with IPC measures. During the study period, 39 patients and 15 staff members became COVID-positive. Within the covid staff, all but one had provided direct care to COVID-positive patients. Overall, behavioral health facilities were largely successful in identifying and quarantining COVID-positive patients. The hospital’s IPC policies/procedures were constantly updated to meet new guidelines and knowledge about the virus, which may have lowered transmission rates and mitigated potential complications. While basic quality and safety of providing psychiatric care were preserved, individual and group therapies’ formats and provision of a therapeutic milieu were altered and may have adversely affected patient care and/or contributed to doubling the length of stay.