Hypersensitivity pneumonitis (HP) lacks specific serum biomarkers for diagnosis, relying instead on clinical course, antigen exposure history, and imaging or pathological findings. However, several biomarkers have been investigated for their potential diagnostic and prognostic utility. KL-6 and SP-D, glycoproteins released during alveolar epithelial injury, are elevated in HP and show seasonal variation, correlating with antigen exposure and avoidance, especially in acute HP. This variation may be a valuable diagnostic tool, particularly in distinguishing HP from other interstitial lung diseases (ILDs). Th1, Th2, and Th17 cytokines contribute to HP pathogenesis, with Th2 chemokines like CCL17 and periostin linked to lung fibrosis and poor prognosis. In contrast, Th1 cytokines such as CXCL9 may protect against disease progression. Other markers, including CA15–3 and sRAGE, also reflect epithelial injury and oxidative stress, providing additional insights into disease mechanisms. While these biomarkers are not specific to HP, they offer significant potential for diagnosis, disease monitoring, and prognosis. Autoantibodies, though uncommon, are associated with poor outcomes in HP. Future large-scale, prospective studies are essential to validate these findings and establish standardized biomarker-based diagnostic criteria for HP.