Mice routinely undergo surgical procedures for use in research; however, studies of skin preparation methods to achieve antisepsis are rare. The present study evaluated 4 skin preparation treatments: depilatory agent followed by povidone-iodine and alcohol scrub; depilatory agent followed by povidone-iodine and saline scrub; electric clippers followed by povidone-iodine and alcohol scrub; and electric clippers followed by povidone-iodine and saline scrub. Swabs for bacterial culture were obtained immediately after hair removal and after scrubbing to measure the reduction in bacterial load. Full-thickness incisions were assigned ASEPSIS wound scores and examined histologically on days 0, 1, and 7 after surgery. Neither bacterial load growth nor ASEPSIS wound scores differed among any of the treatments. Histopathology revealed statistically significant but biologically irrelevant differences. Overall all treatment methods achieved acceptable bacterial load reduction and surgical site healing.