Background: The immune system is increasingly recognized as critical in cancer development, progression, and treatment response. Intense lymphocytic infiltration in pre-treatment biopsies predicts improved survival in TNBC; lymphopenia after RT correlates with poor prognosis in other solid tumors. We investigated the prognostic impact of RT-associated lymphopenia in early-stage TNBC. Methods: Diagnostic and treatment data from electronic medical records of Stanford University Hospital (SU) and Palo Alto Medical Foundation (PAMF), a nearby community practice, were linked at an individual patient level with demographic, staging and survival data from the California Cancer Registry. A Cox proportional hazards model (adjusted for patient age, race, insurance, marital and neighborhood socioeconomic status, and for tumor stage, grade, and chemotherapy receipt) was used to analyze the relationship between immunologic measures obtainable from complete blood counts (CBC) treated as continuous variables (minimum absolute lymphocyte count [ALC], absolute neutrophil count [ANC], and white blood cell count [WBC]) and overall survival (OS). Results: 1211 TNBC patients (pts) seen at SU and/or PAMF were identified from 2000-2011; 218 pts with stage I-III TNBC received adjuvant RT and CBC within 12 months of starting radiation. 190 of these 218 pts (87.2%) received neoadjuvant or adjuvant chemotherapy. 58.3% of treated pts were lymphopenic (ALC < 1.0 K/uL) with median ALC of 0.9 (interquartile range: 0.66-1.23). On multivariable analysis, lower ALC immediately after RT was strongly associated with worse OS (hazard ratio [HR] for death with an increase of 0.1 K/uL in ALC = 0.70, 95% confidence interval [CI]: 0.55–0.91); lower ANC (HR = 0.98, 95% CI: 0.95–1.01) and WBC (HR = 0.99, 95% CI: 0.97–1.00) were not associated with OS. Conclusions: Among curable TNBC pts, a low ALC after RT was independently associated with a substantial increase in the risk of death; no such effect was observed with other blood counts. These results build on tumor-based studies implicating lymphocyte function as a key determinant of treatment response and survival, and may guide development of targeted immunotherapies for TNBC.