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Background The presence in Morocco of Argasid ticks of the Ornithodoros erraticus complex, the vector of tick-borne relapsing fever (TBRF) in North Africa, has been known since 1919, but the disease is rarely diagnosed and few epidemiological data are available. Methodology/Principal Findings Between 2006 and 2011, we investigated the presence of Ornithodoros ticks in rodent burrows in 34 sites distributed across Morocco. We also collected small mammals in 10 sites and we investigated TBRF in febrile patients in Kenitra district. The prevalence of Borrelia infections was assessed by nested PCR amplification in ticks and the brain tissue of small mammals, and by evaluation of thick blood films in patients. A high proportion of burrows were infested with ticks of the O. erraticus complex in all regions of Morocco, with a mean of 39.5% for the whole country. Borrelia infections were found in 39/382 (10.2%) of the ticks and 12/140 (8.6%) of the rodents and insectivores studied by PCR amplification, and 102 patients tested positive by thick blood film. Five small mammalian species were found infected: Dipodillus campestris, Meriones shawi, Gerbillus hoogstrali, Gerbillus occiduus and Atelerix algirus. Three Borrelia species were identified in ticks and/or rodents: B. hispanica, B. crocidurae and B. merionesi. Conclusions/Significance Tick populations belonging to O. erraticus complex are widely distributed in Morocco and a high proportion of ticks and small mammals are infected by Borrelia species. Although rarely diagnosed, TBRF may be a common cause of morbidity in all regions of Morocco., Author Summary In North Africa, Argasid ticks of the Ornithodoros erraticus complex are the only known vector of Borrelia infections causing tick-borne relapsing fever (TBRF) in humans. There is limited data on vector distribution, the animal reservoir of the disease has never been investigated, and there is no published data on TBRF patients. Our aim was to systematically investigate the distribution of O. erraticus s.l. in most regions of Morocco, to measure the proportion of infected ticks, to identify small mammalian species that act as potential reservoir, and to analyze data on TBRF patients fortuitously collected during a malaria eradication program. Our study shows that a high proportion of rodent burrows are colonized by vector ticks in all regions of Morocco from the Atlantic Sahara to the Mediterranean coast. We identified three Borrelia species in ticks and/or small mammals: B. hispanica, B. crocidurae and B. merionesi. We report five species of small mammals found infected for the first time. Our analysis of 102 TBRF patients shows that the disease is strictly seasonal in northwestern Morocco with a maximum incidence during summer. We believe that TBRF, although rarely diagnosed, is a common cause of morbidity in all regions of Morocco.