This study investigated associations between Trypanosoma lewisi and Xenopsylla cheopis, a common cyclical vector of T. lewisi; Polyplax spinulosa, a reported mechanical vector; and Laelaps echidnina and Laelaps lamborni, 2 rodent mites of Rattus norvegicus in Durban, South Africa. In total, 379 R. norvegicus individuals were live-trapped at 48 sites in 4 locality types around Durban during a 1-yr period. Rats were euthanized, cardiac blood was taken to check for hemoparasites, and ectoparasites were removed for identification. Parasite species richness was higher in pups (2.11) and juveniles (1.02) than adults (0.87). Most rats in the study harbored 1 or 2 of the 5 parasites surveyed. Rats with trypanosomes and fleas were more prevalent in the city center and harbor, where juveniles were most affected. Rats with lice were more prevalent in informal settlements and urban/peri-urban areas, where pups had the highest infestations. There was a significant positive association between rats with fleas and trypanosomes and a negative association between rats with lice and trypanosomes. Location and rat age were significant predictors of T. lewisi, X. cheopis, and P. spinulosa. Mites showed no strong association with trypanosomes. Ectoparasite associations are possibly habitat and life-cycle related. We conclude that Durban's city center, which offers rats harborage, an unsanitary environment, and availability of food, is a high-transmission area for fleas and trypanosomes, and consequently a potential public health risk.