Introduction Oral health-related quality of life is a reflection of general health and wellbeing; related problems stand as major public health issues. Aim To investigate the potential association between dental caries and quality of life (QoL) among children aged 5-6 years old. Materials and methods Oral examination of 310 children admitted to a paediatric dentistry clinic was performed by using the International Caries Detection and Assessment System II (ICDAS-II) and the QoL was assessed using the Early Childhood Oral Health Impact Scale. A nested case-control study was conducted with all 104 QoL-unaffected children as the controls and a random sample of 104 QoL-affected children as the cases. Relative risk (RR) and its 95% confidence interval (CI) values were calculated to interpret potential associations. Results Gender distribution was similar by case controls (52.9% vs 51.0% were females, respectively). Early childhood caries (ECC) was detected in 78.8% of cases and 19.2% of controls. In binary analysis of the QoL (with a cutpoint of 2), low parental education, having a sibling, dental visit history for complaints and irregular/no toothbrushing were detected as significant predictors of poor QoL (p value <0.001). The RR of negative impact on QoL was fourfold (95% CI 2.64-5.69) among children having ECC, revealing a significant upward trend of impaired QoL with increasing ICDAS-II scores (t = 13.323; p value <0.001). Conclusion All patients should be evaluated thoroughly for social and psychological problems, besides functional and aesthetic in dental visits.