Objective Anxiety and/or Depressive Disorders (ADDs) and Chronic Somatic Diseases (CSDs) are associated with substantial levels of health-related disability and work impairment. However, it is unclear whether comorbid ADDs and CSDs additively affect functional outcomes. This paper examines the impact of ADDs, CSDs, and their comorbidity on disability, work absenteeism and presenteeism. Methods Baseline data from the Netherlands Study of Depression and Anxiety (n = 2371) were used. We assessed presence of current ADDs (using psychiatric interviews, CIDI) and presence of self-reported CSDs. Outcome measures were disability scores (WHO-DAS II questionnaire, overall and domain-specific), work absenteeism (≤ 2 weeks and > 2 weeks; TiC-P) and presenteeism (reduced and impaired work performance; TiC-P). We conducted multivariate regression analyses adjusted for socio-demographics. Results Both ADDs and CSDs significantly and independently impact total disability, but the impact was substantially larger for ADDs (main effect unstandardized β = 20.1, p < .001) than for CSDs (main effect unstandardized β = 3.88, p < .001). There was a positive interaction between ADDs and CSDs on disability (unstandardized β interaction = 4.06, p = .004). Although CSDs also induce absenteeism (OR for extended absenteeism = 1.42, p = .015) and presenteeism (OR for impaired work performance = 1.42, p = .013), associations with ADDs were stronger (OR for extended absenteeism = 6.64, p < .001; OR for impaired work performance = 7.51, p < .001). Conclusion Both CSDs and ADDs cause substantial disability, work absenteeism and presenteeism, but the impact of ADDs far exceeds that of CSDs. CSDs and ADDs interact synergistically on disability, thereby bolstering the current view that patients with physical mental comorbidity (PM-comorbidity) form a severe subgroup with an unfavourable prognosis.