Samples of African cuttlefish, Sepia bertheloti, were collected from the gulf of Guinea and analyzed using energy dispersive X-ray reflection fluorescence (EDXRF) analytical technique to assess potential toxic elements pollution of the marine environment. Eleven elements, namely, Cl, Sr, K, Ca, Br, Fe, Cu, Zn, Mn, Ni, and Se were detected. It is observed that Cl, K, Ca, Mn, Fe, Cu, and Zn identified in the cuttlefish exceeded their maximum recommended dietary reference intakes for individuals. This is supported by their calculated pollution index (PI > 1) indicating that the cuttlefish might have accumulated the elements via polluted marine environments. Comparison of the elemental composition of the cuttlefish with other common meats showed that the values of Ca, Mn, Ni, Cu, and Zn were comparatively high. Strong and significant positive correlation existed between Cl/Zn; Cl/Br; Ca/K; Se/Ni; Se/Cu; Se/Zn; Br/Cu; Br/Zn; Br/Se; Sr/K; and Sr/Ca signifying a common source or chemical similarity, while no strong and significant negative correlation existed between the elements detected.