Objective: To investigate the relations of the ATP level in the CD4+ T lymphocytes during the infection stage of severe acute pancreatitis (SAP). Methods: Forty-two SAP patients (SAP group) admitted to Nankai Hospital and 36 healthy volunteers (control group) were enrolled in this study. The ATP value in the CD4+ T lymphocytes of the SAP group were measured by ImmuKnowTM assay on day 1, 4, 7, 14 and 21 after admission and the control subjects underwent the same assessment at matched intervals. Afterwards, according to whether the patients entered the infection stage or not, the SAP group was further divided into the infection group (18 cases) and non-infection group (24 cases). The ATP level variations among the 3 groups were analyzed and compared, and the receiver operating characteristic curve was used to assess the value of using the ATP level alteration to estimate the secondary infection of SAP. Results: The ATP in the CD4+ T lymphocytes of the control group maintained a consistent level. The ATP levels of the two SAP groups altered in a roughly parallel pattern, both which increased significantly compared to the control group on day 1 and 4 after their hospitalization (P<0.05), but declined significantly on day 7 and reached the lowest values on day 14, and then picked up gradually. The decreasing extent of the ATP level of the infection group was greater than that of the non-infection group (P<0.05), and the ATP level of the non-infection group was approximately close to that of the control group but the infection group was still significantly lower than the control group (P<0.05). ROC curve analysis showed that the SAP patients would experience an increased risk of secondary infection when their ATP level in the CD4+ T lymphocytes deceased (<151.55 ng/mL), and the sensitivity and specificity of using the ATP level alteration to estimate the secondary infection of SAP were 0.810 and 0.605, respectively. Conclusion: The ATP level in CD4+ cells can relatively reflect the overall cellular immunological competence and the risk to secondary infection for SAP patients.