Abstract Background Eczema, asthma and hay fever are global health problems and their prevalence has increased considerably over the last decades. All appear to share an underlying atopic diathesis but their aetiology is considered to be multifactorial. They have been linked to decreases in health related quality of life (HRQoL) in adults, children/adolescents and/or parents of children. Research also suggests an association of the three conditions with mental health, which in turn is related to HRQoL decreases. We aimed to assess whether the impact of any of the three conditions on HRQoL is modified by presence of mental health problems. Methods The impact of occurrence of the three conditions within the past four weeks and 12 months on HRQoL, as measured by the ‘Quality of Life in Children – Revised’ (KINDL-R) questionnaire was analysed by use of the complex sample general linear model in a population-based sample (N = 6518) of children and adolescents aged 11 – 17. Analyses were adjusted for the other atopic conditions, sociodemographic and clinical variables and stratified for mental health as measured by the Strengths and Difficulties Questionnaire (SDQ) (normal n = 5697, borderline n = 609, abnormal n = 193). Results Eczema and hay fever within the past four weeks were significantly associated with decreased total or certain subscales of KINDL-R after adjusting for all other variables when no mental health abnormalities were present while asthma was associated with better HRQoL in these individuals. However, when mental health problems were present, eczema was positively associated with several subscales and the positive impact of asthma was stronger. The presence of mental health problems accentuated the negative relationship between hay fever and HRQoL (stronger negative impact). However, due to decreasing numbers in the group with mental health problems only few associations reached statistical significance. Conclusions While the results suggest mental health to have a modifying effect on the relationship between some atopic conditions and HRQoL caution needs to be exercised in interpreting the results: First, the groups with borderline or abnormal mental health were comparably smaller than the group with normal mental health. In the group with normal mental health small effects were more likely to become significant than in the other two groups. Secondly some problems regarding the validity of the self-report SDQ still remain.