Nurses play a significant role in providing care and support to patients in the healthcare system. However, their role can often lead to high stress levels and psychiatric distress. This study aimed to examine the impact of socio-demographic, and work-related characteristics, perceived social support, emotional labor, and presenteeism on psychiatric distress among Iranian nurses during the COVID-19 pandemic. This study examined nurses' knowledge, attitudes, use, and acceptance of the use of artificial intelligence in nursing care. This was a cross-sectional survey study. A total of 296 nurses were recruited via stratified random sampling from 9 teaching hospitals in a province in the northwestern region of Iran in 2020. The survey package included socio-demographic and work-related questions, the General Health Questionnaire (GHQ-28), the Dutch Questionnaire for Emotional Labor, the Multidimensional Scale of Perceived Social Support, and the Stanford Presenteeism Scale. Descriptive and multiple regression analyses were performed to examine the associations between nurses' psychiatric distress and potential factors. The mean age of the participants was 29.3 ± 7.6 years, and they were mostly female (50.3%). Psychiatric distress was reported by more than half of the participants (53.8%). Multiple regression analysis revealed that female sex, rotating shift work, contract employment status, less work experience, lower social support, higher emotional labor, and presenteeism were positively related to nurses' psychiatric distress and explained 28.2% of the variance in psychiatric distress among nurses. This study highlights the significant prevalence of psychiatric distress among nursing staff during the COVID-19 pandemic. Targeted interventions are necessary to improve mental health outcomes in this population. To protect nurses against the negative effects of health crises, healthcare organizations must provide a supportive work environment that prioritizes nurses' psychological well-being. Providing nurses with basic support, especially for their preferred shift schedules, and offering contract employees the same benefits as permanent employees, including health insurance, retirement plans, and paid leave, can create a sense of stability and support. Additionally, healthcare organizations should invest in workplace initiatives that promote positive mental health, such as stress management programs and team-building activities.