Host genetic variability is relevant to understanding how parasites modulate natural selection in wild fish populations. Coastal lagoons are transitional ecosystems where knowledge lacks on relationships between genotypic diversity with parasitism. The aim of this study was to assess the effect of genetic diversity on host health and parasitological traits in fish inhabiting a Mediterranean lagoon. Black-striped pipefish were collected in August 2023 and 2024 from the Mar Menor (Iberian lagoon, SE Spain). Genetic diversity was measured as Internal Relatedness (IR: a homozygosity index from microsatellite markers). Population frequency was lower for the medium IR level. For this same category, both health indices (external body condition and internal organs) indicated a worse status. Parasite prevalence, abundance and an index of life-cycle complexity (heteroxenous species) were greater for the medium level of genetic diversity. Such results are explained under a scenario of parasite-mediated disruptive selection: a higher disease pressure against the phenotypically intermediate individuals. Two contrasting strategies were detected to better control parasitism at the host genotypic level: (1) high homozygosity, and (2) high heterozygosity, which probably reflects better immuno-competence as a phenotypic trait. From an evolutionary perspective, parasites play a crucial role in shaping genetic diversity within host populations.