Axillary dissection is a standard surgical procedure for stage III skin and soft tissue tumors and is usually performed under general anesthesia. This study aimed to investigate the feasibility of performing axillary dissection with Serratus muscle plane block plus intravenous sedation. Fifteen patients undergoing axillary dissection were prospectively recruited. The patients were evaluated during their pre-operative anesthetic appointment, during their procedure, and at post-operative days 1 and 30. The blockade was performed superficial to the Serratus muscle at the level of fourth rib. Sedation was performed using propofol, fentanyl, dexmedetomidine, and S-ketamine. None of the patients required conversion to general anesthesia. Surgeons showed a highly positive response when asked about the anesthetic technique, and most of them found the technique “indistinguishable” from general anesthesia. The median (interquartile range) pain scores at rest over all time frames was 0 (0-0). Furthermore, no patients developed nausea, hemodynamic instability, or any complications associated with the technique. The Serratus plane block associated with intravenous sedation proved feasible for axillary lymphadenectomy, however, further clinical trials should evaluate potential advantages compared to other techniques.