Lionfish (Pterois spp.) are invasive species reported since 2009 in the Corales del Rosario y San Bernardo National Natural Park in the Caribbean. Their capture and consumption are strategies to control their dispersion and limit ecological damage. The natural park is influenced by the vicinity of Cartagena's residential, industrial, and touristic activities, as well as sediments loaded with mercury from the Dique Channel. For the first time, total mercury levels in muscle from 58 lionfish were determined, with values ranging from 0.01 to 0.38 μg/g (mean = 0.11 ± 0.01 μg/g). Fish length ranged from 17.4 to 44.0 cm (mean = 28.0 ± 0.63 cm). Mercury levels did not increase proportionally to fish length for pooled data, but the relationship was significant for specimens from Rosario Island. Mercury levels comply with legislation for fish consumption, but the risk to human health may appear if it occurs daily. Therefore, precautionary approach and a permanent monitoring strategy are strongly advised.