Objective To analyze the variations of procalcitionin (PCT) and red blood cell distribution width (RDW) in premature infants with septicemia and to investigate their values in evaluating the severity and prognosis of septicemia. Methods A retrospective study was conducted to analyze the medical records of 96 premature infants diagnosed with septicemia and admitted to the First Affiliated Hospital of Anhui Medical University from December 1, 2014 to December 1, 2018. According to the severity of the disease and neonatal shock score, there were 42 cases selected to the severe septicemia group (severe clinical condition with shock, shock score >6 points) and 54 in the mild septicemia group (mild clinical condition without shock or shock score ≤6 points). Moreover, after three days' treatment, they were divided into two groups: death group (n=10) and survival group (n=86, survived during hospitalization). Peripheral venous blood samples were collected before and on the first and third day after treatment to detect PCT and RDW. Dynamic changes of the two indexes were compared between different groups. Mann-Whitney U test, Wilcoxon rank sum test, Friedman test or receiver operating characteristic (ROC) curve was used for statistical analysis. Results (1) Before and on the first and third day after treatment, the severe septicemia group had a higher level of PCT than the mild group [3.7 (0.4-37.3) vs 1.4 (0.2-5.0) ng/ml, 43.1 (18.7-83.0) vs 17.1 (4.1-34.6) ng/ml, 26.1 (3.8-67.3) vs 4.8 (0.3-32.9) ng/ml; Z=-2.017, -3.350 and -2.932; all P<0.05]. In both groups, PCT level on the first day after treatment was the highest, and that on the third day after treatment was higher than that before treatment (all P<0.05). On the first and third day after treatment, RDW in the severe group was higher than that in the mild group [16.5% (16.2%-18.6%) vs 16.3% (15.5%-17.3%), 16.1% (15.5%-19.4%) vs 15.7% (15.1%-16.5%); Z=-1.992 and -2.165; both P<0.05]. In the severe and mild groups, RDW on the first day after treatment was higher than that before and on the third day after treatment; in the mild group, RDW on the third day after treatment was lower than that before treatment, while in the severe group, RDW on the third day after treatment was higher than that before treatment (all P<0.05). (2) On the first and third day after treatment, PCT and RDW in the death group were higher than those in the survival group [PCT: 162.0 (62.9-187.2) vs 19.9 (4.3-46.1) ng/ml, 122.6 (65.0-180.8) vs 6.2 (0.5-32.9) ng/ml; Z=-4.114 and -4.594; RDW: 18.4% (16.9%-21.2%) vs 16.3% (15.7%-17.2%), 21.8% (20.6%-22.2%) vs 15.8% (15.2%-16.5%); Z=-3.307 and -4.831; all P<0.05]. In both groups, PCT on the first day after treatment was higher than that before and on the third day after treatment, and the level on the third day after treatment was higher than that before treatment (all P<0.05). In the death group, RDW on the first and third day after treatment were higher than that before treatment, and RDW on the third day after treatment was higher than that on the first day; in the survival group, RDW on the first day after treatment was higher than that before treatment, but on the third day after treatment, it was lower than that before and on the first day after treatment (all P<0.05). (3) The cut-off values of PCT for predicting severe septicemia in premature infants before and on the first and third day after treatment were 3.475, 29.765 and 3.460 ng/ml, respectively, and the sensitivity and specificity were 54.8% and 75.9%, 69.0% and 72.2%, and 83.3% and 46.3%, respectively. The cut-off values of PCT for predicting the death of premature infants with septicemia on the first and third day after treatment were 40.595 and 64.855 ng/ml, respectively, with the specificity of 73.3% and 87.2% and sensitivity of both 100.0%. The predictive thresholds of RDW for severe septicemia on the first and third day after treatment were 15.650% and 18.300%, respectively, and the sensitivity and specificity were 95.2% and 29.6%, 33.3% and 92.6%, respectively. The predictive thresholds for death were 16.650% and 18.450%, and the sensitivity and specificity were 100.0% and 68.6%, 100.0% and 91.9%, respectively. Conclusions Dynamic monitoring of PCT and RDW levels may help with early diagnosis, determination of severity and prognosis prediction of severe septicemia in premature infants. Key words: Neonatal sepsis; Calcitonin; Erythrocyte indices; Infant, premature; Prognosis