OBJECTIVE: Nearly 80% of cancer patients struggle with insomnia, which is associated with decreased heart rate variability (HRV) and quality of life (QOL). The aim of this secondary analysis was to evaluate the possible effects of Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI), delivered during chemotherapy visits, on QOL and HRV in patients with breast cancer (BC). METHOD: QOL and HRV data were obtained during a pilot clinical trial assessing the feasibility and effects of BBT-CI on insomnia. A total of 71 BC patients (mean age = 52.5 years) were randomly assigned to either BBT-CI or a healthy-eating control intervention (HEAL). BBT-CI and HEAL were delivered over 6 weeks (2 face-to-face sessions plus 4 phone calls) by trained staff at 4 National Cancer Institute-funded Community Oncology Research Program clinics. QOL was measured with the Functional Assessment of Cancer Therapy (FACT-G) and HRV with the Firstbeat device at baseline and after intervention. RESULTS: There were significant improvements in QOL after intervention for BBT-CI (FACT-G, p = .009; FACT-B, p = .016; ANCOVA) and 5-min supine HRV measures (SDNN, p = .005; rMSSD, p = .004; HF, p = .009; ANCOVA) compared with HEAL. CONCLUSIONS: Patients randomized to BBT-CI showed improvements in QOL and HRV, providing support for BBT-CI's possible benefit when delivered in the community oncology setting by trained staff. A more definitive efficacy trial of BBT-CI is currently being planned with sufficient statistical power to evaluate the intervention's clinical utility. (PsycINFO Database Record (c) 2019 APA, all rights reserved).