Trypanosomosis is a serious constraint to livestock productivity in sub-Saharan Africa. Chemotherapy which is the main means of control is unsatisfactory because of drug resistance and toxicity. Thus, the search for alternative antitrypanosomal agents has become imperative. The study was aimed at evaluating the effects of astaxanthin alone or in combination with diminazene aceturate (DZ) on parasitaemia and haematological parameters in Trypanosoma brucei brucei–infected Wistar rats. Eighty Wistar rats were divided into eight groups of ten rats each and treated as follows: I, DW (uninfected and treated with distilled water); II, S/OIL (uninfected and treated with soya oil); III, T (infected with 106 trypanosomes/mL); IV, PreA [pretreated with astaxanthin (100 mg/kg)] + T; V, PreA + T + DZ (3.5 mg/kg); VI, T + A (astaxanthin); VII, T + A + DZ; VIII, T + DZ. Parasitaemia was monitored daily, and blood was collected for evaluation of haematological parameters at the end of the experiment. Parasitaemia increased progressively in the T, PreA + T and T + A groups till the termination of the experiment, but was lower (P < 0.05) in the PreA group alone, compared to the T and T + A groups at days 6 and 8. There was a resurgence of parasitaemia in 10% of rats in the T + A + DZ group at day 7 post-treatment. The red blood cell counts, PCV and haemoglobin concentration were higher (P < 0.05), but lower neutrophil and total leucocyte counts (P < 0.05) in PreA and/or DZ groups compared to the T and T + A groups. Rats in the T and T + A groups had higher (P < 0.05) erythrocytic indices. Pre-treatment with astaxanthin and/or diminazene aceturate was more effective than post-treatment in decreasing parasitaemia and ameliorating the anaemia caused by T. brucei brucei infection in Wistar rats.