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OBJECTIVES: Analyze miRNA and mRNA expression in patients with bloodstream infection (BSI) caused by Candida albicans (CA) and non-albicans Candida spp. (CNA).PATIENTS/METHODS: We prospectively enrolled 20 adults with candidemia (10 CA and 10 CNA) and 22 hospitalized controls without sepsis but with comparable comorbidities. miRNA and mRNA expression were determined by next-generation sequencing (NGS), and differentially expressed miRNAs were validated by qPCR. Integrated miRNA-mRNA and KEGG/Reactome enrichment analyses were used to predict miRNA targets and identify perturbed pathways.RESULTS: NGS detected seven dysregulated miRNAs in CA vs. controls. qPCR confirmed marked overexpression of miR-125a-5p and miR-99b-5p in CA compared with CNA and controls. No miRNAs were differentially expressed between the CNA and control groups. RNA-Seq revealed that 22, 111, and 152 genes were differentially expressed in CA vs. controls, CNA vs. controls, and CA vs. CNA, respectively. Enrichment analysis highlighted cell-cycle and DNA-replication programs in both species groups, while CA uniquely affected histidine/phenylalanine metabolism. Integrated mapping linked upregulated miR-125a-5p to repression of pro-apoptotic and immune-modulatory genes, whereas miR-99b-5p targeted cell-cycle checkpoint genes.CONCLUSIONS: Overexpression of miR-125a-5p and miR-99b-5p in whole blood may discriminate C. albicans candidemia. These miRNAs are promising rapid biomarkers and targets for antifungal therapy.