Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological emergencies. The role of cytokines and chemokines in the pathogenesis, progression of the disease, and histopathologic features is not fully elucidated. To address this gap, we conducted a retrospective study examining the associations between 42 serum biomarkers, histopathologic findings, and clinical outcomes in SJS/TEN patients. We reviewed the medical records of 23 patients diagnosed with SJS/TEN. Regarding histopathology, our study did not reveal any significant associations between the degree of epidermal necrosis, dermal mononuclear cell infiltration, and clinical outcomes. However, an intriguing observation was made regarding the degree of dermal infiltration of CD8 + cells, which showed a negative correlation with the severity of acute ocular complications. Notably, serum levels of IFN-γ positively correlated with the number of CD8 + cells in dermal infiltration. Additionally, higher serum levels of myeloperoxidase were associated with greater degrees of epidermal necrosis, while serum Fas ligand and stem cell factor levels were elevated in individuals with increased dermal mononuclear cell infiltration. Furthermore, the levels of S100A8/A9 were significantly correlated with the SCORTEN and mortality rate. These findings provide insights into the intricate pathogenesis of the disease.