What we already know about this topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Clusters of differentiation 39 and 73, enzymes expressed on the surface of regulatory T cells, promote cancer recurrence and metastasis by suppressing immune cells. The authors hypothesized that propofol is less immunosuppressive than volatile anesthetics. The objective of this randomized trial was to compare the changes in cluster of differentiation 39 and 73 expression on regulatory T cells between propofol- and sevoflurane-based anesthesia during breast cancer surgery. Methods: A total of 201 patients having breast cancer surgery were randomly assigned and analyzed (n = 99 for propofol, n = 102 for sevoflurane). Blood samples were obtained immediately before anesthesia induction and 1 and 24 h postoperatively. The frequency of cluster of differentiation 39 and 73 expression on circulating regulatory T cells (primary outcome) and the frequency of circulating type 1 and type 17 helper T cells, natural killer cells, and cytotoxic T cells were investigated. Serum cytokines and the neutrophil-to-lymphocyte ratio were also evaluated. Results: Changes in cluster of differentiation 39 and 73 expression on regulatory T cells over time did not differ with propofol and sevoflurane groups (difference [95% confidence interval]: 0.01 [-2.04 to 2.06], P = 0.995 for cluster of differentiation 39; -0.93 [-3.12 to 1.26], P = 0.403 for cluster of differentiation 73). There were no intergroup differences in type 1, type 17 helper T cells, natural killer cells, cytotoxic T cells, cytokines, or the neutrophil-to-lymphocyte ratio. Conclusions: Changes in immune cells were similar with propofol and sevoflurane during breast cancer surgery. The effect of anesthetics on the perioperative immune activity may be minimal during cancer surgery.