Distinguishing between disease-induced and drug-associated hyponatremia is important in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. This study aimed to characterize the specific reporting profile of linezolid (LZD)-associated hyponatremia using the Japanese Adverse Drug Event Report (JADER) database. Data from the JADER database (April 2004‒May 2025) were analyzed. Crude reporting odds ratios (cRORs) for hyponatremia were calculated to confirm the safety signal for LZD. Subsequently, multivariate logistic regression and Weibull distribution analyses were performed for LZD-associated cases to explore demographic factors associated with the reporting and temporal reporting profiles, respectively. Among 4,480 reports of hyponatremia, 117 were associated with anti-MRSA agents (LZD, tedizolid, vancomycin, teicoplanin, daptomycin, and arbekacin). LZD demonstrated a significant reporting signal for hyponatremia (cROR, 10.04; 95% confidence interval [CI], 8.19–12.31). This signal persisted even in the oral administration subgroup (cROR, 3.41; 95% CI, 1.83–6.38). The multivariate logistic regression analysis restricted to LZD-associated cases identified age ≥ 70 years (adjusted reporting odds ratio [aROR], 1.73; p < 0.001) and female sex (aROR, 1.52; p < 0.05) as demographic factors associated with the reporting. The median time to onset was 5.5 days. The Weibull shape parameter (β) was 1.34, indicating an increasing reporting hazard profile over time during the acute treatment period. These hypothesis-generating findings suggest that cumulative exposure to LZD may lead to hyponatremia, supporting the need for careful serum sodium monitoring, particularly in elderly and female patients.