The effect of a hyperimmunized (GLOBIGEN®) hen egg yolk-based product was evaluated for the control of diarrhea caused by enterotoxigenic Escherichia coli (ETEC) F4 and F18 in newly weaned piglets. The negative control (NC) animals were not challenged and received 40 ppm of colistin as a growth promoter, 2300 ppm of zinc, and 150 ppm copper. The other three treatments were all challenged with ETEC F4 and F18: 0.2% GLOBIGEN®, 4% dry porcine plasma (DPP), and a positive control (PC). Animals on GLOBIGEN® does not differ from NC (p > 0.05) in weight gain. They also had better feed efficiency than DPP (p < 0.05). Animals in GLOBIGEN® did not present diarrhea as was seen in DPP and PC. GLOBIGEN® also showed reduced F4 and F18 (p < 0.05) excretion compared to PC. The results of this study suggest that GLOBIGEN® acts efficiently in diarrhea control, being a viable alternative to the use of antibiotics in newly weaned piglets.