Objective: To investigate the effect of a pediatric syrup containing Amoxicillin on resin-based on the surfaces of resin-based materials under pH cycling. Material and Methods: Cylindrical samples (n=60) of a compomer (Freedom) and a microhybrid composite (TPH Spectrum) were prepared following the manufacturer's instructions. The specimens were divided into two groups and treated for 30min, twice a day, for 14 days with a pediatric syrup containing Amoxicillin, Amoxil™ 500mg/5ml (experimental group) or Distilled water (control group). During the 14 days, the samples were submitted to pH cycling (3h in demineralizing, 20h in remineralizing saliva, and 1h for treatment). The surface roughness was evaluated at baseline, on the 7 th and 14 th days of erosive challenge using a profilometer and illustrated by SEM. The data were statistically analyzed by one-way ANOVA, Tukey HSD and paired T-tests (p < 0.05). At baseline, the mean Ra TPH = mean Ra F (p > 0.05). Results: After 7 days, it was observed no erosion (p = 0.674) for THP Spectrum (0.19 Ra) and an increasing of Ra (p = 0.02) for Freedom (19.95 Ra). After 14 days, it was observed an increasing of Ra for both THP Spectrum (0.56 Ra) and for Freedom (3.44 Ra), demonstrating that the degradation was treatment and time-dependent (p < 0.001). The pediatric syrup containing Amoxicillin increased the surface roughness of the TPH Spectrum surface one and a half times (p = 0.003) and the surface roughness of Freedom was increased by more than two times (p < 0.001). SEM images showed different aspects of the surfaces of the two materials with a loss of integrity to both. Conclusion: The pediatric syrup containing Amoxicillin under pH cycling increased the roughness of the both tested resin-based restorative materials.