Sepsis is a life-threatening condition triggered by infection, resulting in widespread inflammation, immune dysfunction, and multiorgan failure. Despite advances in medical science, early detection, treatment, and prognosis remain significant challenges. In this study, we investigated the expression and functional role of ZDHHC19, a palmitoyltransferase enzyme, in sepsis. Our results demonstrate that ZDHHC19 is significantly upregulated in neutrophils during sepsis and correlates with inflammatory pathways critical to disease progression. High ZDHHC19 expression was associated with increased activation of immune-inflammatory processes such as collagen metabolism, myeloid cell activation, and cell adhesion, while suppressing antigen presentation. Additionally, ZDHHC19 expression was linked to poor patient prognosis, with higher levels correlating with increased mortality and sepsis shock. Using advanced computational tools, including XGBoost for machine learning-based core gene selection and CellChat for cell communication analysis, we identified key regulatory networks modulated by ZDHHC19, revealing its pivotal role in immune dysregulation. These findings suggest that ZDHHC19 may serve as a potential biomarker for the diagnosis and prognosis of sepsis and open new avenues for targeted therapeutic interventions aimed at modulating immune responses in this condition.