The immune modulating activity of β-glucan on aquatic species has been a matter of intense investigation. Here, we aimed to investigate the effect of β-glucan on wound healing of silver catfish, a Neotropical South American scale-free fish. Small sections of skin and muscle (3 mm in diameter) were removed and fish were bathed daily with β-glucan (0.1% and 0.5%) up to 28 days when cicatrization was complete. A group of fish similarly injured and non-exposed to β-glucan was used as control. Wound closure and healing was monitored visually and by histopathological analysis. In fish bathed with 0.5% β-glucan we found reduced blood cortisol levels at day one post-wounding and, by day 7 post wounding, the deposition of granulation tissue was higher compared to non-exposed fish. In addition, from day 7 forward, wound size was significantly lower in fish bathed with 0.5% β-glucan. Histopathological analysis of the wounded site indicated a thin layer of immature epidermal cells at day one post wounding. A discrete inflammation with mixed inflammatory cell infiltrate was observed on wounded muscle and was lower by day 7 post wounding on fish bathed with 0.5% β-glucan. By day 14 post wounding, the deposition of collagen fibers and the presence of fibroblast and new muscle fibers were higher in fish exposed to 0.5% β-glucan, and dermis restoration was complete. Thus, our results indicate that in silver catfish wound healing occurs rapidly and improves greatly by daily bathing with β-glucan.