The aim of the present study was to assess whether mothers' sense of coherence (SOC) was a predictor of decline in oral health-related quality of life (OHRQoL) of preschoolers. A 3-year cohort study was conducted in Diamantina, Brazil. At baseline, 162 preschoolers aged one to three years were randomly selected from among children registered in local Primary Healthcare Units. In the first stage, mothers completed a sociodemographic questionnaire, the Brazilian version of the Early Childhood Oral Health Impact Scale (B-ECOHIS), and the Brazilian short version of the Sense of Coherence Scale (SOC-13). The total score obtained from the SOC-13 was used to select exposed and unexposed children. Clinical examinations were performed to detect the presence of dental caries, traumatic dental injury, and malocclusion. At follow-up, mothers completed the sociodemographic questionnaire and the B-ECOHIS again. The incidence of severe dental caries and adherence to the proposed treatment at baseline were evaluated. A decline in OHRQoL was considered if there was an increase in the B-ECOHIS score of at least one unit. The chi-square test and Poisson regression were performed. A total of 151 preschoolers participated in the study, among whom 37.7% showed a decline in OHRQoL. Mothers' SOC was not associated with a negative impact on OHRQoL (RR = 1.24; 95%CI = 0.81-1.88), while the incidence of severe dental caries had a greater impact on the decline in OHRQoL (RR = 2.02; 95%CI = 1.29-3.16). Mothers' low SOC was not a predictor of decline in the OHRQoL of preschoolers after a 3-year follow-up period.