Docetaxel-induced fluid retention (DIFR) cumulatively occurs and is one of the most troublesome adverse effects. This study aimed to determine whether high dose dexamethasone (DEX) could prevent DIFR during breast cancer treatment. Breast cancer patients receiving docetaxel (75 mg/m2)-containing regimens were divided into 4 and 8 mg/day DEX groups, with each DEX dose administered on days 2–4 and retrospectively assessed. Incidence of greater than or equal to grade 2 DIFR was significantly lower in the 8 mg group (13.0%) compared to the 4 mg group (39.6%,P= 0.001). All-grade DIFR was also less in the 8 mg group (P= 0.01). Furthermore, the maximum variation of body weight was significantly lower in the 8 mg group (P= 0.0003). These results were also confirmed in the propensity score-matched population. Additionally, time-related DIFR incidence was also significantly delayed in the 8 mg group (P= 0.0005). Our study revealed that high dose DEX prevents DIFR. Therefore, further studies on its management are required for less onerous chemotherapy provision with better DIFR control.