The prevalence of blood group antigens and phenotypes varies significantly in Brazil. To ensure a proper rare blood supply, it is essential to establish a local and regional database of rare donors connected to the national registry. The objective of this study was to create a database of rare blood donors in the northern region of southern Brazil. From November 2011 to December 2018, red blood cell (RBC) phenotyping and genotyping were performed on common and high-prevalence antigens in donors and patients in southern Brazil. During this study period, 17 patients and 33 blood donors with rare phenotypes were identified. Six patients had already been alloimmunized to clinically significant antigens. Patients with the following phenotypes (i.e., negative for high-prevalence antigens) were found: Yt(a–), Jk(a–b–), Lu(a–b–), O_h (Bombay), Tc(a–), k–, and Fy(a–b–). Among the donors, Kp(a+b–), Fy(a–b–), Lu(a–b–), and k– phenotypes were identified. We also found four donors with the weak D type 18 phenotype. In conclusion, we observed that the prevalence of rare blood phenotypes in our region corresponds more to the prevalence found in the Caucasian population when compared with other regions in Brazil. Our results show the importance of continuous screening for rare donors in different regions of the country and the creation of a local database to support RBC transfusions in patients who need rare blood.