This study investigated the hepatic and neural effects of TiO₂ nanoparticle and Pb in Hoplias malabaricus trophically exposed. The alanine transaminase activity was altered at the high dose of exposed group to Pb and at the lowest doses of co-exposed groups. It may reflect the hepatic effects of TiO₂ on Pb toxicity, but the aspatate transaminase activity was not altered. The decreased injury index observed at the highest dose of co-exposed group compared to TiO₂ may be related to the increased energy demand and can explain the more pronounced toxic effects observed in this group. The liver authomethallography revealed the metals presence at high dose groups. Serotonin concentration increased at the Pb lowest dose and at the highest dose of co-exposed group compare to control. Most importantly, when associated the contaminants were able to interact and altered some biomarkers. However, further studies, about action mechanisms of this co-exposure are needed.