Abstract: OBJECTIVE To explore the clinical value of serum CD40 ligand (CD40L) and high-mobility group box 1 (HMGB1) in diagnosis of bloodstream infections in the hematological tumor and chemotnerapy patients complicated with agranulocytosis and fever. METHODS A total of 200 hematological agranulocytosis patients complicated with fever who were treated in the First People's Hospital of Kashgar Prefecture from Nov. 2020 to Nov. 2023 were enrolled in the study and were divided into the infection group with 57 cases and the no infection group with 143 cases according to the status of bloodstream infections. The levels of serum CD40L and HMGB1 were detected by ELISA. Multivariate logistic regression analysis was performed for risk factors for the bloodstream infections. The values of serum CD40L and HMGB1 in diagnosis of bloodstream infections were evaluated by ROC curves, and the clinical practicability was determined by decision curves. RESULTS The age, proportion of patients with hypoalbuminemia, proportion of patients treated with central-line catheter indwelling, proportion of patients with diarrhea, proportion of patients treated with no less than 3 types of antibiotics, and levels of procalcitonin (PCT), CRP and HMGB1 were higher in the infection group than in the no infection group, while the serum CD40L of the infection group was lower than that of the no infection group (P＜0.05). Logistic regression analysis showed that the central-line catheter indwelling(OR=4.185) and rise of HMGB1 level(OR=6.842) were the risk factors for the bloodstream infections in the patients with hematological agranulocytosis(all P＜0.001), the risk of CD40L level (OR=0.523,P=0.022)was a protective factor for the bloodstream infections. The AUC of the joint detection of CD40L and HMGB1 was 0.857 in diagnosis of bloodstream infections, greater than that of the single detection of CD40L or HMGB1(all P＜0.05). The net benefit rate of the joint detection of serum CD40L and HMGB1 is superior to the single detection of serum CD40L or HMGB1 in diagnosis of bloodstream infections in the hematological agranulocytosis patients complicated with fever when the high-risk threshold value ranged between 0.10 and 0.95. CONCLUSIONS The hematological tumor and chemotnerapy patients complicated with fever and bloodstream infections show the decline of serum CD40L and the rise of HMGB1, and the joint detection of the two indicators has high diagnostic value.