This study investigated the influence of occupational stress and social relationship at the workplace on the psychological wellbeing of nurses and midwives in the Catholic Health Service of the Western Region of Ghana. A cross-sectional descriptive study was employed for the study. A sample of 300 nurses and midwives was used for the investigation. A questionnaire based on Nurses' Occupational Stress Scale was adopted to measure occupational stress among the nurses and midwives and Ryff's Psychological Wellbeing Scale (PWB 18 items) to measure psychological wellbeing among nurses and midwives and the Worker Relationship Scale developed by Biggs, Swailes and Baker was used to measure social relationships at the workplace. For statistical analysis, Linear Regression Analysis for statistical purposes. The study’s result indicated that occupational stress explained 18.1% psychological wellbeing variances. It was also found that occupational stress predicted psychological wellbeing among nurses and midwives in the Catholic Health Service of the Western Region. The study’s result further revealed that social interaction and experiences among health professionals (nurses and midwives) at the workplace significantly determine their psychological wellbeing. It was recommended that nurses and midwives should be trained on better ways of dealing with occupational stress in order to stay psychologically sound.