PURPOSE: Malaria remains a major global health challenge, particularly in sub-Saharan Africa and low- and middle-income countries (LMICs), contributing substantially to mortality and morbidity rates. In resource-limited settings, access to specialized diagnostic tests is often restricted, making basic blood analysis a valuable diagnostic tool. This study investigated the correlation between malaria infection and full blood count values in a rural region of Ghana during the 2022 rainy season, aiming to highlight diagnostic insights available from routine blood analyses. METHODS: A retrospective case-control analysis was conducted on 544 confirmed malaria cases, comparing their blood values with those of matched malaria-negative controls. RESULTS: Parasitaemia levels peaked during the rainy season, with July showing the highest values. Malaria-positive patients exhibited lower levels of haemoglobin, white blood cells, lymphocytes, and platelets, but higher neutrophil counts compared to controls. Middle-aged women had significantly lower haemoglobin levels than men, and younger individuals showed higher parasitaemia levels. A negative correlation was found between Plasmodium density and haemoglobin and platelet counts, while positive correlations were observed with white blood cell and neutrophil counts. CONCLUSION: This study highlights the significant burden of malaria in rural Ghana during the rainy season and underscores the impact of infection on blood values. Routine full blood count analysis provides a practical and accessible diagnostic tool in resource-limited settings. The findings emphasise the importance of targeted interventions for high-risk groups, particularly children and women, to improve patient management and reduce malaria-related morbidity.