During the production of snake antivenoms, the animals used as immunoglobulin source are subjected to processes that could deteriorate their physical condition. Therefore, these conditions must be carefully designed and validated. In this work, the immunization and bleeding protocols applied to horses used to produce the African polyspecific antivenom EchiTAb-plus-ICP were evaluated regarding their effects on the horses' health. The study focused on horses that had been previously immunized with venoms and then received periodic booster venom injections for antivenom production. It was found that the periodic immunization with 5 mg of a mixture of venoms ofBitis arietans,Echis ocellatus,Dendroaspis polylepis,andNaja nigricollisdid not induce systemic signs of envenomation, and only caused mild swelling at the injection site, which did not evolve to abscesses, fistulas, or fibrosis. Three consecutive days of bleeding, collecting 6–8 L of blood per day, and self-transfusing the red blood cells (RBC) in the second and third days, did not induce evident cardiorespiratory alterations. However, this procedure caused significant reductions in RBC, hematocrit, hemoglobin, and total plasma protein values. Seven weeks after bleeding, these parameters were recovered, and horses were ready for the next immunization/bleeding cycle. The intravenous administration of equine albumin, at a dose of 2 g/kg body weight, increased the apparent plasma volume and the albumin concentration. However, this procedure induced early adverse reactions and transient alterations of the serum levels of the enzyme gamma-glutamyl transferase (GGT), thus suggesting some degree of hepatic injury. It was concluded that immunization and bleeding as described in this work do not cause significant clinical alterations in the horse's health, except for a transient drop in some hematological parameters. The albumin-based fluid therapy used does not hasten the recovery after bleeding but instead induces adverse events in the animals.