The salmon industry’s challenges with skin health and sea lice emphasize the necessity for fish-sensitive measures like functional nutrition to boost skin health and fish welfare. The present study investigated the efficacy of krill meal (KM) for skin mucosal health and sea lice in Atlantic salmon (170 g). Following an 8-week feeding period, in duplicate tanks, on test diets (8% KM, 12% KM, and the control group), fish underwent a 2-week sea lice challenge, reaching 350 g. The 8% KM diet group had thicker skin epithelium (72.3 µ) compared to the 12% KM (51.3 µ) and the control groups (43.8 µ) after 8 weeks. Additionally, skin mucosal health parameters—cell size (208 µ2), cell density (25.2%), and defense activity (1.19)—were significantly enhanced with 8% KM compared to the 12% KM (cell size: 162.3 µ2, cell density: 17%, defense activity: 1.04) and the control group (cell size: 173.5 µ2, cell density: 16.4%, defense activity: 0.93). Furthermore, fish fed with 8% KM significantly showed the lowest sea lice, along with reduced cell size while maintaining a high abundance of skin mucous cells, suggesting efficient turnover of the skin mucosal layer to remove sea lice effectively. This study highlights the potential of KM as part of a functional nutrition strategy to enhance skin mucosal health and mitigate sea lice challenges.