Little is known about the effects of common daily experiences in patients with major depressive disorder (MDD). The Daily Hassles and Uplifts Scale (HUPS) was assessed in 142 treatment-naïve adult MDD outpatients randomized to 12 weeks of treatment with either antidepressant medication (ADM) or Cognitive Behavior Therapy (CBT). Three HUPS measures were analyzed: hassle frequency (HF), uplift frequency (UF), and the mean hassle intensity to mean uplift intensity ratio (MHI:MUI). Remission after treatment was not predicted by these baseline HUPS measures and did not moderate outcomes by treatment type. In contrast, HUPS measures significantly changed with treatment and were impacted by remission status. Specifically, HF and MHI:MUI decreased and UF increased from baseline to week 12, with remission leading to significantly greater decreases in HF and MHI:MUI compared to non-remission. ADM-treated patients demonstrated significant improvements on all three HUPS measures regardless of remission status. In contrast, remitters to CBT demonstrated significant improvements in HF and MHI:MUI but not UF; among CBT non-remitters the only significant change was a reduction in HF. The changes in HUPS measures are consistent with how affective biases are impacted by treatments and support the potential value of increasing attention to positive events in CBT.