Ovine GM-CSF (Granulocyte–Macrophage Colony-Stimulating Factor, CSF2) is a hematopoietic cytokine belonging to the colony-stimulating factor family, which also includes G-CSF (CSF3) and M-CSF (CSF1) that regulate the development, proliferation, and activation of myeloid immune cells. In sheep (Ovis aries), GM-CSF is produced by activated T lymphocytes, macrophages, endothelial cells, fibroblasts, and epithelial cells in response to infection, inflammatory cytokines, or immune stimulation. Ovine GM-CSF binds to the GM-CSF receptor (CSF2R) expressed on hematopoietic progenitor cells and mature myeloid cells, activating intracellular signaling pathways such as JAK/STAT, MAPK/ERK, and PI3K–AKT, which promote the proliferation and differentiation of granulocytes, macrophages, and dendritic cells, while enhancing their phagocytic and antigen-presenting functions. In ovine immunity, GM-CSF contributes to host defense against bacterial and parasitic infections, particularly through activation of macrophages and neutrophils in tissues such as the lungs and gastrointestinal tract. Sheep are also used as animal models for studying respiratory and inflammatory diseases, and GM-CSF–regulated myeloid responses have been investigated in ovine models of respiratory syncytial virus (RSV) infection, which closely resemble human infant RSV disease, helping researchers understand immune mechanisms driving viral lung inflammation and evaluate potential therapeutic strategies.