<p>Aspergillosis includes a range of illnesses caused by <i>Aspergillus</i> species, primarily affecting individuals with weakened immune systems. Blood metabolites are gaining attention as potential biomarkers for diagnosing and managing diseases, but their causal role in aspergillosis risk remains unclear. This study used Mendelian randomization (MR) to explore potential causal associations between blood metabolites, their ratios, and aspergillosis risk. Single-nucleotide polymorphisms (SNPs) associated with metabolites were selected as instrumental variables. The primary analysis was conducted using the inverse variance weighted (IVW) method, with sensitivity analyses to ensure robustness. The study identified several metabolites and ratios significantly associated with aspergillosis risk. Elevated levels of 2-linoleoylglycerol, palmitoleate, serotonin, and 3-indoxyl sulfate were linked to increased risk, while higher levels of myristate, 1-methylhistidine, and theobromine were associated with reduced risk. Findings were validated using a secondary dataset, and reverse MR analysis confirmed the directionality from metabolites to disease. These results shed light on the metabolic underpinnings of aspergillosis and may inform future research on diagnostic and therapeutic strategies.</p>