Background: The global disease burden attributable to mental and neurological disorders has been increasing over the years. World Health Organization (WHO) recommends the integration of mental health services into existing primary healthcare framework as one strategy for dealing with the burden. Understanding the attitudes of nurses towards people with mental illness is important for a successful integration and management outcome of patients.Aim: This study aimed to determine primary healthcare nurses’ attitudes towards people with mental illness.Setting: The study was conducted at Greater Lobatse health district, one of the primary healthcare districts in Botswana.Methods: A cross-sectional study was conducted among 202 nurses working in the greater Lobatse health district from 01 May 2023 to 30 November 2023. Convenience sampling was used. Data were collected using a structured self-administered questionnaire.Results: The prevalence of negative attitudes was 51.5%. The mean age (standard deviation [s.d.]) of respondents was 33.4 (8.0) years. Being a non-specialised nurse (B= –0.184; p = 0.014), having a personal history of mental illness (B = –0.215; p = 0.002), and having poor knowledge about mental illness (B = –0.149; p = 0.032) were associated with negative attitudes.Conclusion: More than half of the respondents have negative attitudes towards people with mental illness. This justifies the need for training and educational programmes and anti-stigma campaigns among primary healthcare nurses to mitigate negative attitudes.Contribution: This study provides insight into primary healthcare nurses’ attitudes towards people with mental illness.