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Objectives To determine the prevalence of malaria parasite carriage and anaemia among senior high school students and to identify the demographic, behavioural and residential factors associated with these outcomes.Design Cross-sectional study.Setting Participants were enrolled from Tempane Senior High School students in the Tempane District of the Upper East Region of Ghana.Participants 290 senior high school students aged 15–22 years.Primary and secondary outcome measures Demographic characteristics, residential status and insecticide-treated bed net (ITN) use were collected using a structured questionnaire. Venous blood samples were obtained for malaria parasite detection by microscopy and haemoglobin measurement. Association analysis was performed using logistic regression models.Results The prevalence of malaria parasite carriage was 23.1%, while 49.0% of participants were anaemic. Day students had a significantly higher prevalence of malaria (59.2%) than boarding students (15.8%) (p<0.001). Malaria parasite infection was also more common among students who did not use ITNs (39.7%) compared with users (5.0%) (p<0.001). In multivariate analysis, not using ITN (adjusted OR (aOR)=15.97; 95% CI 6.33 to 40.32; p<0.001) and being a day student (aOR=5.65; 95% CI 2.58 to 12.36; p<0.001) were significant predictors of malaria parasite infection. Students infected with malaria parasites had significantly lower mean haemoglobin (11.50±1.43 g/dL) than uninfected students (12.56±1.35 g/dL) (p<0.001). Malaria parasite infection (aOR=9.36; 95% CI 3.91 to 22.42; p<0.001) and male students (aOR=2.26; 95% CI 1.09 to 4.65; p=0.028) were associated with higher odds of anaemia. Whereas age groups 18–20 years (aOR=0.41; 95% CI 0.17 to 0.97; p=0.043) and those above 20 years (aOR=0.07; 95% CI 0.02 to 0.27; p<0.001) were associated with lower odds of anaemia.Conclusion Malaria and anaemia remain prevalent among senior high school students in the Upper East Region of Ghana, with asymptomatic malaria strongly linked to anaemia. Not using ITN and being a day student significantly increased the odds of malaria parasite infection. These findings underscore the need to extend malaria prevention interventions to adolescents through school-based programmes, including routine screening, treatment and promotion of consistent ITN use, especially among day students.