Mouse Interferon-Alpha (IFN-α) is a type I interferon comprising multiple closely related subtypes produced primarily by plasmacytoid dendritic cells and virus-infected cells in mice (Mus musculus), where it serves as a critical mediator of early innate antiviral immunity. Upon binding to the type I interferon receptor complex (IFNAR1/IFNAR2), murine IFN-α activates JAK/STAT signaling pathways, leading to induction of interferon-stimulated genes (ISGs) that inhibit viral replication, enhance antigen presentation, promote natural killer (NK) cell cytotoxicity, and shape adaptive immune responses. Mouse IFN-α is central to experimental models of viral infections including influenza virus, lymphocytic choriomeningitis virus (LCMV), murine cytomegalovirus (MCMV), West Nile virus, and SARS-CoV-2 (adapted strains), where timing and magnitude of interferon responses strongly influence viral control and immunopathology. Dysregulated or chronic IFN-α signaling has also been implicated in murine models of systemic lupus erythematosus, autoimmune disease, cancer, and interferonopathies. IFNAR-deficient and IFN-α transgenic mouse models have been instrumental in dissecting type I interferon biology, antiviral mechanisms, and immune-mediated tissue damage. As both a biomarker and functional regulator of host–pathogen interactions, mouse IFN-α remains central to preclinical research on antiviral therapies, vaccine development, cancer immunotherapy, and immune modulation strategies relevant to human disease.