More instability (MSSD) and variability (SD) of negative affect (NA) have been related to current and future depressive symptoms. We investigated whether NA instability and variability were predictive of the rate of symptom improvement during treatment and of reaching remission status. Forty-six individuals with major depressive disorder completed six days of ecological momentary assessments (10 beeps/day) before starting a combination of pharmacotherapy and supportive therapy. During and after treatment, the Hamilton Depression Rating Scale (HDRS) diagnostic interview was performed monthly for 18 months. The rate of change in HDRS scores over five months (during treatment) and remission status (HDRS ≤ 7) over eighteen months were predicted by the SD, MSSD and Mean of NA, and relevant baseline predictors. Higher Mean NA and baseline symptom severity, but not NA variability or instability, predicted stronger depressive symptom reduction during treatment. Higher odds of remitting were only associated with lower Mean NA. Higher mean NA may indicate more room for improvement and thus for a steeper rate of symptom change, while lower mean NA levels may imply that remission status is more readily reached. To resolve the inconclusive findings for instability and variability as predictors of symptom improvement replication in larger samples is required.