Objective This study aimed to explore the association of JKAP with sepsis risk and investigate its correlation with disease severity, inflammatory cytokines, and survival in sepsis patients. Methods A hundred and one sepsis patients along with 100 healthy controls were enrolled, and their blood serum samples were collected for JKAP and inflammatory cytokines measurement by enzyme-linked immunoassay. The difference in serum JKAP between sepsis patients and healthy controls was determined. Among sepsis patients, the correlation of JKAP with disease severity, laboratory indexes, inflammatory cytokines, 28-day mortality, and accumulating survival was analyzed. Results JNK pathway-associated phosphatase level was decreased in sepsis patients compared with healthy controls and presented with good value in predicting decreased sepsis risk (AUC = 0.896 [95% CI: 0.851-0.941]). And its low expression was associated with advanced disease severity (APACHE II score and SOFA score) and systemic inflammation (CRP, PCT, TNF-alpha, IL-1 beta, IL-6, and IL-17) in sepsis patients. Additionally, JKAP level was decreased in deaths compared with survivors and had good value in distinguishing deaths from survivors (AUC = 0.742 [95% CI: 0.636-0.849]). Further, Kaplan-Meier curve analysis disclosed that JKAP high expression predicted more prolonged accumulating survival in sepsis patients. Conclusion JNK pathway-associated phosphatase is of good value in predicting lower sepsis risk, and its downregulation correlates with advanced disease severity, higher level of systemic inflammation, and poor survival in sepsis patients.