Plasmodium falciparum predominates as the leading cause of malaria-related mortality, particularly in sub-Saharan Africa, posing a significant global health threat. This study aims to assess the hematological and biochemical alterations attributed to P. falciparum infection among patients seeking care in health facilities across Northern Local Government Areas of Taraba State, encompassing Jalingo, Lau, and Zing. A prospective cross-sectional study method was adopted and enrolled 1,500 participants who underwent testing for P. falciparum using Giemsa-stained blood film examination, Rapid Diagnostic Test (RDT), and Polymerase Chain Reaction (PCR). Hematological parameters, including Packed Cell Volume (PCV), white blood cell counts, and erythrocyte sedimentation rate (ESR), as well as biochemical markers such as albumin, bilirubin, and electrolyte levels, were assessed. Results shows that, out of 1,500 individuals, 304 were infected with P. falciparum, representing a prevalence of 20.3%. Significant differences were observed in hematological and biochemical parameters between infected and non-infected participants, including lower PCV and platelet counts, elevated neutrophil counts, and altered liver enzyme levels among parasitized individuals. The study also compared the diagnostic performance of RDT and microscopy, revealing variations in sensitivity and specificity. This study underscores the clinical utility of hematological and biochemical parameters in malaria management, particularly in resource-limited settings like Nigeria. The findings highlight the importance of comprehensive diagnostic approaches and suggest integrating these adjunct tools into malaria treatment protocols to enhance patient care and outcomes. Keywords: Malaria, Derangement, Haematological, Biochemical, Plasmodium falciparum