Whereas the amplitude of the startle reflex varies with stimulus valence in the normal population, a lack of this affective modulation has been reported in patients with major depressive disorder. The present study sought to clarify blunted startle modulation as a feature of depression by comparing 16 patients diagnosed with major depression prior to and after 2 weeks of SSRI treatment, and 16 healthy controls. The affect-modulated startle reflex paradigm and the Self-Assessment Manikin were used to probe affective reactivity. In addition, a preliminary analysis of change in affective reactivity pattern was performed with depressed patients who could be assessed in the eighth week of treatment (n = 13). The control group showed a linear trend in response across valence categories, which was stable over sessions. Blunted affective reactivity was observed only in the patients and persisted after 2 weeks of treatment. Nevertheless, a linear trend could be detected in the eighth week of treatment. These findings confirm that the affective reactivity is blunted in depression and provide initial evidence for the lack of change in the early phase of SSRI antidepressant treatment. Nevertheless, in a small group, the emergence of a linear trend in response was evident later with treatment. Large-scale studies are required to assess the relation between the treatment response and the change in affective modulation of the startle reflex, as a potential biomarker.