Major-depressive-disorder (MDD) and alexithymia have both been associated with empathy deficits. We examined whether depression and alexithymia show dissociable or interacting effects on cognitive and emotional trait and state empathy. Healthy controls with high and low alexithymia and MDD-patients with high and low alexithymia were assessed. We used the Interpersonal–Reactivity-Index-questionnaire (IRI) for trait cognitive and emotional empathy and the Multifaceted-Empathy-Test (MET) for state cognitive and emotional empathy. Firstly, we found a main effect of alexithymia, irrespective of depression, on trait and state cognitive empathy: High alexithymia subjects showed lower scores in perspective taking (IRI) and in the cognitive-empathy-component of the MET. Secondly, we found main effects of alexithymia and depression on trait emotional empathy (IRI-subscale personal distress). Moreover, we found a significant depression-by-alexithymia-interaction on trait emotional empathy: MDD-patients showed particularly high personal distress when affected by alexithymia (IRI). Thirdly, alexithymia and depression had no impact on state emotional empathy (MET). However, analyzing positive and negative trials separately, we found more emotional empathy in MDD-patients concerning negatively valenced stimuli. Our data suggest dissociable and interacting effects of MDD and alexithymia on empathy. Importantly, except for heightened personal distress, empathy deficits in MDD-patients were entirely due to concurrent alexithymia.