Objective To investigate the effect of different depths of anesthesia on postoperative cognitive dysfunction (POCD) and inflammatory cytokines in children. Methods Sixty children aged 6-8 years who underwent orthopedic surgery in Wenzhou Integrated Traditional Chinese and Western Medicine Hospital from July 2017 to September 2018 were selected. According to different anesthetic depths, they were divided into three groups: group A [intraoperative bispectral index (BIS) maintained at 50-59], group B (intraoperative BIS maintained at 40- 49) and group C (intraoperative BIS maintained at 30-39), with 20 cases in each group. The MMSE scale and MoCA scale were used to evaluate the incidences of POCD in the three groups 1 day before operation and on the 1st, 3rd and 7th days after surgery. And the serum levels of IL-6, IL-10 and S-100β in the three groups of children were detected 1 day before operation, at the end of operation, and 1, 3 and 7 days after operation. Results Analysis of variance using repeated measurement design showed that there were differences in MMSE and MoCA scores at different time points (P < 0.05), there were also differences in MMSE and MoCA scores among the three groups (P < 0.05), there were differences in the change trends of MMSE and MoCA scores among the three groups (P < 0.05). On the 1st and 3rd days after operation, there was no significant difference in the incidence of POCD among the three groups (P > 0.05). There were differences in serum levels of IL-6, IL-10 and S-100β protein at different time points (P < 0.05), there were differences in serum levels of IL-6, IL-10 and S-100β protein among the three groups (P < 0.05), and there were also differences in the change trends of serum IL-6, IL-10 and S-100β protein levels among the three groups (P < 0.05). Conclusions Low anesthesia depth (BIS maintained at 50-59) can decrease the levels of inflammatory factors and the incidence of POCD in children after general anesthesia and reduce brain damage.