The aim of this study was to determine the levels of some trace metals in water from Cross River estuary (CRE) and estimate the human health risk associated with water from the estuary via ingestion pathway and dermal contact. The trace metals in water were determined using atomic absorption spectrophotometer and the human health risk assessment of the trace metals was carried out using models stipulated by United States environmental Protection Agency (USEPA). The range for the results in mg/l was as follows: Pb (0.193- 0.632), Cd (0.118 - 1.084), Ni (0.048 -0.632), Fe (0.056 - 0.921), Zn ( 0.063 - 0.242), Cu(0.072 - 0.146). All the investigated metals were above the WHO limit except zinc and copper. The target hazard quotient (THQ) via ingestion pathway for Pb, Cd and Ni were higher than unity. Also, the hazard indices for all the investigated metals in all the study sites were higher than unity. The target hazard quotient and Hazard index via dermal pathway were less than one for all the metal investigated, except Cd at Ebughu. Regular monitoring and minimization of anthropogenic activities resulting in elevated metal concentration is recommended.