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Introduction: Coronavirus disease 2019 (COVID-19) affects physical and mental health of patients. This study aimed to investigate the psychological distress, level of hope, and the role of families of patients with COVID-19 in the Fangcang shelter hospital (FSH) and explore potential influencing factors. Methodology: We conducted an online observational cross-sectional study on 397 patients with mild to moderate COVID-19 from two FSH in Shanghai, China from 12 April to 16 May 2022. The questionnaire included demographic information, distress thermometer (DT), family adaptation, partnership, growth, affection, resolve (APGAR) index, and the Herth hope index (HHI). Results: The patients reported symptoms of severe psychological distress (n = 109, 27.46%) and low levels of family care (n = 152, 38.29%). More than half of the patients (n = 244, 61.46%) exhibited high levels of hope, and around one-third of the patients (n = 151, 38.04%) reported moderate levels of hope. The study noted a significant negative correlation between the scores for psychological distress and APGAR and a significant positive correlation between the scores for APGAR and HHI (p < 0.05). The FSH living experience, diet, and symptoms of COVID-19 were closely associated with psychological distress among patients (p < 0.05). Conclusions: Patients with COVID-19 living in the FSH reported high levels of symptoms of psychological distress and low levels of family care, but relatively high levels of hope. Health care workers should improve the living and eating conditions in the FSH, strengthen family support, and alleviate the COVID-19 related symptoms of patients. [ABSTRACT FROM AUTHOR]