Babesia microti is a red cell parasite that is endemic in the Northeastern and upper Midwestern regions of the US and responsible for the disease referred to as babesiosis. The parasite is most often transmitted by the bite of a deer tick but may also be transmitted by blood. Infection may be asymptomatic or cause non-specific symptoms: fever, fatigue, headache and muscle pain, or in some cases severe disease in those with a compromised immune system, hemoglobin-related diseases (such as sickle cell disease) or those lacking a spleen. The Red Cross began blood donation screening under an investigational protocol in June 2012 in the New England area and upper Midwest. Donors who consented for investigational screening were tested by two tests: an individual donation NAT assay (polymerase chain reaction, PCR) and an antibody assay, the latter using an automated indirect immunofluorescence assay (IFA). Reactive donations were further tested by various methods to confirm infection including more sensitive PCR methods and western blot. The frequency of detecting an infected donor in an endemic area where screening had occurred was about 1 per 300 donations using both antibody and NAT. In the absence of screening, the risk of transfusion-transmitted babesiosis is generally about 1 per 100,000 unscreened donations in an endemic state but maybe as high as 1 per 18,000 in highly endemic areas. Unscreened blood in a highly endemic area is 16 times more likely to be infectious than screened blood (where screened blood has not been associated with a transmission). In May 2018, the Red Cross began testing from whole blood samples using a NAT assay, now FDA licensed, that detects ribosomal RNA of the parasite following red cell lysis, thereby greatly increasing sensitivity and obviating the need for antibody testing; because the lysis step releases thousands of copies of babesia RNA, mini-pool testing can be performed (MPs of 16). If a reactive donation is identified, testing is repeated, and a sample is sent for antibody testing by IFA. In May 2019, the FDA released guidance to test all donations collected in the following states considered babesia endemic or contiguous to an endemic state: Maine, Vermont, New Hampshire, Connecticut, Massachusetts, New York, New Jersey, Delaware, Rhode Island, Maryland, Pennsylvania, Virginia, Minnesota, and Wisconsin and in the District of Columbia. Red Cross will implement the guidance testing in May 2020.