Background: The use of endocrine therapy (ET) in post-menopausal breast cancer patients may affect their cognitive status. This study aims to assess the effects of tamoxifen and aromatase inhibitors (AIs) on quality of life (QoL) and cognitive functions in breast cancer patients. Patients and Methods: The study included 101 patients receiving tamoxifen, 97 patients receiving AIs, and 95 patients without any ET. All patients completed both the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the Short Form-12 (SF-12) questionnaires. Results: The patients' characteristics were similar between the groups. The mean duration of ET was 2.6 years for tamoxifen and 2.5 years for Als. EORTC QLQ-C30 global scores and cognitive functioning scores as well as SF-12 mental scorings (mcs) were found not significantly different between patients without any ET and those receiving tamoxifen or AIs (p = 0.529, p = 0.333, and p = 0.452, respectively). SF-12 mcs correlated moderately with EORTC QLQ-C30 global scores for the 3 treatment groups (all p values < 0.001). Conclusion: Our study suggests that QoL and cognitive functions are similar in patients receiving Als or tamoxifen. Moreover, it appears that these parameters also do not differ in patients with respect to the use of ET.