Pancytopenia is seen in late HIV infection; it is associated with medical complications and with decreased survival. We determined the prevalence of pancytopenia at baseline in a cohort of HIV-positive Hispanics living in Puerto Rico, and compared their socio-demographic, immunological and clinical characteristics. A total of 1202 patients enrolled between 2000 and 2010 were included. They were grouped according to pancytopenia status, defined by having: platelets <150,000 μL, white cell count <4000 μL, and hemoglobin <12 g/dL (women) or <13 g/dL (men). Differences were evaluated using Student’s t-test, Chi-square test and Kaplan-Meier method. The prevalence of pancytopenia was 8.7%. Patients with pancytopenia had lower BMI and lower CD4 count, as well as higher HIV viral load and higher proportions of unemployment, clinical AIDS and antiretroviral treatment (ART) use (p < 0.05). One-year mortality rate was significantly higher in patients with pancytopenia (18.1% vs. 5.1%, p < 0.001). When stratifying for ART this association persisted for patients who did not receive ART (41.4% vs. 5.2%, p < 0.001), but it was not seen in patients who received treatment (9.2% vs. 5.6%, p = 0.196). Pancytopenia was associated with elements of advanced stages of HIV. ART could reduce the mortality of HIV-patients with pancytopenia to levels comparable to patients without the disorders.