Background: Pivalate-conjugated β-lactam antibiotics (PCAs) have been developed to enhance bioavailability by incorporating the pivoxil group into the β-lactam chemical structure. Although there are only case reports and observational studies limited to pediatric patients on PCA-associated hypocarnitinemia, no comparisons have been made across all age groups, and comprehensive data from larger-scale studies are limited. Therefore, we investigated the association between PCA use and the onset of hypocarnitinemia for all age groups by analyzing the Japanese Adverse Drug Event Report (JADER) database. Methods: We analyzed 2,226,010 adverse event cases from the JADER database between April 2004 and March 2024. To detect signals of hypocarnitinemia, we calculated the reporting odds ratio and 95% confidence interval. Results: Among the total reported cases of hypocarnitinemia, the highest number of occurrences (252 cases) and the signal of hypocarnitinemia were detected in PCAs, whereas no cases were observed for other β-lactam antibiotics (non-PCAs). Multiple logistic regression analysis revealed that the PCA use, age (< 10 years), and concomitant use of valproate were associated with the onset of hypocarnitinemia. Most patients with hypocarnitinemia were under 10 years of age. An evaluation based on consumption data analysis from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) open database suggested that antimicrobial consumption is highest among children under 10 years of age. Conclusions: Our findings suggest that the use of β-lactam antibiotics containing a pivoxil moiety is disproportionately associated with reports of hypocarnitinemia in the JADER database. These findings should be interpreted as hypothesis-generating.