Oxidative stress contributes to haemolytic anaemia in many species including dogs and cats, as well as in humans. Red cells are exposed to a continual oxidant challenge, both endogenously from within the red cells themselves and also exogenously from other tissues, and from ingested or administered oxidants. When the oxidative challenge exceeds the antioxidant provisions of the red cell, damage occurs in the form of lipid and protein peroxidation, cytoskeletal crosslinking, oxidation of haemoglobin to methaemolglobin, and precipitation of denatured sulphhaemoglobin as Heinz bodies. These deleterious sequelae produce fragile red cells with reduced lifespan, and result in poorer oxygen delivery to tissues, intravascular haemolysis, anaemia, haemoglobinuria and jaundice. A number of features increase the risk of oxidant damage in dogs and cats. Thus dog red cells have low levels of the antioxidant enzyme catalase. Cat haemoglobin has at least four times as many readily oxidizable thiol residues compared to most species, whilst their hepatic capacity for glucuronidation is much reduced, which can result in greater accumulation of oxidants. Like humans, both species may also be exposed to excess oxidants from systemic diseases such as diabetes mellitus, hepatic lipidosis, hypophosphataemia and neoplasias. Iatrogenic oxidants include drugs such as acetaminophen and other non-steroidal anti-inflammatory compounds. Ingested toxins include heavy metals, particularly important in dogs with their increased propensity for scavenging. Ingestion of feeds containing products from Allium species of plants has also long been associated with red cell oxidative damage and Heinz body formation in both dogs and cats. Though less common than in humans, there are occasional congenital enzyme deficiencies which reduce the enzymatic oxidant defence of the red cells in these species. Treatment usually relies on removal of the oxidant challenge or support against the resulting anaemia. Specific antioxidants currently lack efficacy but analogy with human medicine suggests that a range possible antioxidants may be potentially beneficial.