Introduction <p>Occupational health and safety are major concerns for health workers worldwide. Nurses working in resource-constrained areas are at higher risk of occupational hazards. The purpose of the study was to assess the knowledge, attitudes, and practices of nurses in a regional hospital in a resource-constrained area towards occupational health and safety.</p> Methods <p>A descriptive cross-sectional survey was conducted using self-administered questionnaires among 136 nurses at a regional hospital in Ghana. The nurses were recruited from five hospital units using simple random sampling. The data were analysed using SPSS, where descriptive and inferential statistics were applied. Knowledge, attitude, and practice items were measured on a four-point Likert scale. Mean scores were computed for all the items in each domain, with higher mean scores indicating a favourable response towards occupational health and safety measures. A one-way analysis of variance (ANOVA) was conducted to compare mean Knowledge, attitude, and practice scores across demographic variables. A Post hoc analysis was conducted for variables with statistically significant scores. Additionally, Pearson correlation analysis was conducted to examine the relationships between knowledge, attitude, and practice (KAP) scores. All statistical tests were two-tailed, and the level of significance was set at <i>p</i> &lt; .05.</p> Results <p>The study findings show that the participant had a high level of knowledge (94.1%) and a positive attitude (80.9%) towards occupational health and safety measures. However, practice was very low, with only 30.9% of the nurses demonstrating good occupational health and safety practices. The correlation analysis revealed a statistically significant positive relationship between knowledge and attitude (<i>r</i> = .507, <i>p</i> &lt; .01), knowledge and practice (<i>r</i> = .433, <i>p</i> &lt; .01), and attitude and practice (<i>r</i> = .656, <i>p</i> &lt; .01). Additionally, a between-subject one-way ANOVA showed a statistically significant difference in knowledge [F(3,132) = 4.05, <i>p</i> = .009], attitude [F(3,132) = 7.18, <i>p</i> &lt; .001], and practice [F(3,132) = 3.91, <i>p</i> = .010] based on level of education. However, there were no significant differences in knowledge, attitudes, and practices regarding occupational health and safety measures across demographic characteristics.</p> Conclusion <p>The study’s findings indicate poor practices towards occupational health and safety. The management of health facilities and health regulatory authorities should institute measures, such as refresher training and monitoring systems, to promote occupational health and safety practices. Safety protocols should also be developed, and nurses should be encouraged to follow them.</p>