Sea lice challenges in the salmon industry highlight the urgent need for fish-sensitive alternative control measures, like functional nutrition, to minimize handling and promote fish health and welfare. The present study investigated the efficacy of krill meal (KM, 8% and 12%), towards reducing sea lice infestation and enhancing skin mucosal health in Atlantic salmon smolts (average weight: 170g). Following an 8-week feeding period on test diets (two doses of KM and a control diet mimicking conventional feed), the fish underwent a 2-week sea lice infestation challenge while maintaining the test diets, reaching an average weight of 350g. After 8-week pre challenge feeding, fish fed with 8% KM diet exhibited a thicker skin epithelial layer (72.3 µ) compared to the 12% KM (51.3 µ) and control groups (43.8 µ). Additionally, skin mucosal health parameters, including cell size (208 µ), cell density (25.2%), and defense activity (1.19), were significantly enhanced with 8% KM compared to control (cell size: 173.5 µ, cell density: 16.4% and defence activity:0.93) and 12% KM (cell size:162.3 µ, cell density: 17% and defence activity: 1.04). Further after the 2-week sea lice challenge the 8% KM-fed fish had statistically significantly the lowest number of sea lice (median of 6.5 per fish) in comparison to 12% KM and control groups (median of 9 per fish). In addition, 8% KM group exhibited a significant reduction in skin mucus cell size while maintaining a high abundance of mucous cells indicating a rapid production and turnover of skin mucosal layer for effectively "washing off" lice. This study, for the first time, highlights the potential of KM as a part of functional nutrition strategy for mitigating sea lice challenges in Atlantic salmon. However, further studies are warranted to explore the biological pathways and mechanisms underlying the observed results.