PURPOSE: Depression prior to breast cancer and its effect on post-diagnosis quality of life in women undergoing breast reconstruction is relatively unknown. The BREAST-Q has become widely used to assess pre- and post-operative patient-reported outcomes. There are no studies evaluating the impact of a pre-cancer diagnosis of depression or anti-depressant use on BREST-Q scores. We investigated if depression or anti-depressant use may alter the results of the BREAST-Q. METHODS: This study is a single-center, retrospective analysis of 300 patients with completed BREAST-Q data who underwent breast reconstruction from November 2013 to 2016 following a diagnosis of breast cancer. Patients completed the BREAST-Q at four time points: pre-operatively, 6-weeks following tissue expander insertion, and 6- and 12-months following final reconstruction. We reviewed medical records to identify patients who had a pre-cancer diagnosis of clinical depression and anti-depressant medication use. Patients were stratified into a depression and no depression group. The depression group was defined as a pre-cancer diagnosis of depression. The no depression group was defined as no pre-cancer clinical diagnosis of depression and no anti-depressant use. BREAST-Q scores were compared between depression (n=50) and no depression (n=250) patients; the depression group was further stratified by anti-depressant (n=36) and no anti-depressant (n=14) use. The Mann-Whitney U test was used for continuous variables, based on the non-parametric distribution of the data. The same statistical guidelines were used for the sub-group analysis. RESULTS: Sexual well-being scores at the 6-week tissue expander follow up for patients in the depression group (median=37, IQR = 25–47) were significantly lower (p<0.01) than scores for patients in the no depression group (median=47, IQR = 39–60). Patients in both groups showed a decrease from baseline in BREAST-Q scores across all domains at the 6-week tissue expander follow-up. However, the scores after final reconstruction (6 and 12-month follow-ups) were higher than baseline for both groups of patients. There were no statistically significant differences in BREAST-Q scores in other domains. The sub-group analysis comparing the depression group on anti-depressant medication (n=36, 72%) to those on no anti-depressant medication (n=14, 28%) did not show any statistically significant differences in BREAST-Q scores across all domains. Six (17%) of the 36 patients with a prior diagnosis of depression were currently taking either bupropion or mirtazapine, two medications that have shown to have minimal effects on sexual function. These patients had clinically higher sexual well-being BREAST-Q scores at baseline (median=61) compared to patients taking anti-depressants that cause sexual dysfunction (median=53). CONCLUSION: Patients with a diagnosis of depression prior to breast cancer had lower BREAST-Q sexual well-being scores at the 6-week tissue expander follow-up, regardless of anti-depressant medication use. While at 6-weeks there is a difference in scores between the patients with depression and no depression, by 12 months no other differences are noted.