We investigated the trophic transfer potential of CuO-NPs from Artemia salina to Amatitlania nigrofasciata. The Cu uptake was investigated by exposure of the instar II nauplii to 0, 1, 10, and 100 mg/L CuO-NPs for 4 h. Dietborne exposure of fish larvae to CuO-NPs was done for 21 days through feeding with pre-exposed nauplii. Thereafter, all survived fish were fed for 21 more days with non-contaminated nauplii. The results showed that NPs could be taken up by nauplii in a concentration-dependent manner. The highest uptake of Cu by nauplii was found to be 50.5 ± 1.4 mg/g dry weight at 100 mg/L. The copper accumulation in fish larvae increased significantly with increasing Cu content in pre-exposed nauplii to different concentrations of CuO-NPs (p < 0.05). At the end of the depuration phase, although the Cu elimination was significantly higher in fish that were fed with more contaminated nauplii, but the survival rate, average final weight, and length of those larvae was still significantly less than the control group (p < 0.05). The accumulated Cu after the depuration phase in cichlid larvae was 25.4 ± 0.5, 29 ± 8.0, 33.9 ± 9.7, and 42.3 ± 4.0 μg/g dry weight at 0, 1, 10, and 100 mg/L of CuO-NPs-treated Artemia. The current findings indicated the ability of manufactured CuO-NPs to be transferred from one trophic level to the next as assessed in the simple food chain consisting of pre-exposed A. salina and A. nigrofasciata.