The objective was to determine the significance of surgical trauma in dermal wound healing. Using intravital microscopy, we analyzed the healing kinetics of full-thickness dermal wounds in the ears of SKH1 mice. Partial hepatectomy (pHx) simulated major surgical trauma, while laparotomy only served as a sham operation (sham). Animals without abdominal surgery served as controls (control). Laparotomy wounds were analyzed for biomechanical qualities and collagen deposition. Morphological characterization of skin repair was performed by histology/immunohistochemistry. In vitro cell assays assessed the paracrine effects of surgical stress. PHx caused a transient increase in tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 levels and led to weight loss, reflecting the host's overall response to surgery. Wound closure in pHx animals was delayed vs. control and sham animals, as indicated by significantly lower values of epithelialization and neovascularization over 10 days. Ear wound histology further revealed a provisional wound matrix with a reduced microvessel density. Moreover, pHx-laparotomy wounds showed a reduced bursting strength coexisting with significantly decreased collagen content. PHx and sham serum caused a significant alteration in in vitro fibroblast viability. Skin healing is dependent on the extent of surgery and is influenced by its paracrine effects. Therefore, considerable effort should be focused on the development of strategies limiting surgery-associated perturbations of dermal repair.