The clinical presentation overlap between malaria and COVID-19 poses special challenges for rapid diagnosis in febrile children. In this study, we collected RNA-seq data of children with malaria and COVID-19 infection from the public databases as raw data in fastq format paired end files. A group of six, five and two biological replicates of malaria, COVID-19 and healthy donors respectively were used for the study. We conducted differential gene expression analysis to visualize differences in the expression profiles. Using edgeR, we explored particularly the expressed genes in different phenotype groups relative to the healthy samples where 1084 genes and 2495 genes were differentially expressed in the malaria samples and COVID-19 samples respectively. Highly expressed genes in the COVID-19 samples were associated with biological processes such as cell division (CCDC124) and SLC12A5-AS1 a lncRNA gene associated with NK-cell while in the malaria samples were associated with biological processes such as immune response (CTSL), T cell activation (RSAD2) and proteolysis (LAP3). By comparing both malaria and COVID-19, the overlaps of 62 differentially expressed genes patterns were identified. Among the shared genes, the hemoglobin complexes and lipid mediators are highly expressed. We found six genes such as CYB5R3, RSAD2, ALOX15, HBQ1, HBM and PNPLA2 associated with malaria and COVID-19 diseases in children, which can be further validated as potential biomarkers. Our study provided new insights for further investigation of the biological pattern in hosts with malaria and COVID-19 coinfection.