Fish provide high-quality protein and essential nutrients. However, environmental pollution can lead to the accumulation of toxic substances such as mercury (Hg), with known negative impacts on human consumers. The aim of this study was to assess fish health and potential human health risks by analyzing the presence of nematodes, Hg concentrations, and liver pathology in freshwater fish from La Mojana, Colombia. For this purpose, 326 specimens were collected. Parasitic infection was evaluated using parasitological indices. Total Hg (T-Hg) was quantified using a direct mercury analyzer. Liver pathology was assessed through histopathological examination. Risk-based fish consumption limits were established by calculating the hazard quotient (HQ) and safe consumption limits. The overall prevalence and abundance of nematodes (Contracaecum sp.) were 46% and 2.72 ± 0.47 parasites/fish, respectively. Sternopygus macrurus exhibited the highest prevalence (100%) and parasite abundance (13.5 parasites/fish) during the rainy season, whereas Hoplias malabaricus demonstrated the greatest prevalence (100%) and abundance (14.8 parasites/fish) in the dry season. The average T-Hg was 0.31 ± 0.01 µg/g ww. During the rainy season, S. macrurus had the highest T-Hg levels (0.46 ± 0.08 µg/g ww); in the dry season, Cynopotamus magdalenae showed the highest T-Hg concentration (0.54 ± 0.03 µg/g ww). Significant positive relationships were recorded between T-Hg and parasite abundance, while these were negative with the condition factor. All specimens exhibited hepatic alterations. The HQ and Hg values suggest potential health risks from frequent fish consumption, especially in fish-dependent communities. These findings highlight the need for precautionary measures by health and environmental authorities to safeguard human and ecosystem health.