Analysis of human serum proteome is found to be very useful for the identification of potential disease-related markers, understanding disease pathogenesis and host immune response since various serum proteins exhibit rapid alteration in expression pattern in response to diseased conditions and show direct correlation with disease progression [10] . In recent years, a number of proteomic studies have been carried out to investigate the pathogen induced alterations in human serum/plasma proteome in different infectious diseases including dengue [11] , SARS [12] , leishmaniasis [13] , and leptospirosis [14] . In this study we have investigated the alterations in human serum proteome due to the P. falciparum infection for obtaining mechanistic insight about the disease pathogenesis and host immune response in the most virulent form of human malaria. Additionally, serum proteome changes in FM were compared with vivax malaria (VM); another widely distributed human malaria to study the similarities and differences in host responses against these two major plasmodial infections. To achieve this comparative analysis we have utilized selected dataset of our previous serum proteomics study on VM [15] , while additional proteomics and immune-assay-based experiments were performed using a bigger (compared to our previous report) clinical cohort of VM patients. The comparative study on FM and VM revealed that quite a few serum proteins associated with diverse essential physiological pathways, including acute phase response signaling, cytokine and chemokine signaling, complement cascades and blood coagulation are commonly altered in both of the plasmodial infections, while some uniquely modulated candidates such as calcium binding protein 39, calpain 10, regulator of G-protein signaling 7, serum paraoxonase/arylesterase, transthyretin in FM and ceruloplasmin, vitamin D-binding protein, serum amyloid P, alpha-2-macroglobulin, fibrinogen beta chain precursor in VM, were also identified. Recently, we performed serum proteomic alterations in another clinically relevant infectious disease, leptospirosis [14] . To evaluate the specificity of the identified protein targets and eliminate the generic febrile responses; expression level of the serum proteins differentially expressed in plasmodial infections (compared to the healthy subjects) was analyzed in leptospirosis patients from our previous study [14] . Another major intention of this present study was identification of the characteristics marker proteins, which can readily discriminate malaria patients (FM from VM as well) from healthy population as well as closely related infectious diseases with high accuracy. The potential serum protein biomarkers identified in our study were used to build statistical models, which successfully classified and predicted the clinical phenotypes of controls (healthy and febrile), FM and VM in a blinded study.