The duration of rapid salinity change (RSC) prevailing in estuarine and coastal regions is increasing due to extreme climate and weather events, posing significant challenges to marine bivalves. The Hong Kong oyster (Crassostrea hongkongensis), an ecologically and economically important species in tropical estuarine ecosystems, has experienced increasing mass mortality during prolonged periods of RSC, yet little is known about underlying physiological processes. Here, we investigated how physiological energetics of C. hongkongensis were affected by longer-lasting scenarios and four-week episodes of RSC. Compared with ambient conditions with seawater salinity ranging from 15 to 20, rapid salinity change by ± 10 units significantly decreased the survival of oysters, with RSC-induced hyposaline stress (-10) resulting in more serious consequences than that of hypersaline regime (+10). Continuing exposure of oysters to both RSC scenarios significantly affected their feeding activities, but the food absorption efficiency were still virtually unchanged. Significantly depressed respiration and increased excretion activities were observed in RSC-stressed oysters, resulting in significantly lowered O:N ratio. Overall, when exposed to RSC, oysters showed significantly decreased scope for growth, due to shifts in energy budget toward maintenance of essential physiological processes. Our results demonstrate the vulnerability of estuarine oysters to prolonged RSC events, and underscore the pressing need to develop strategies to enhance oyster tolerance under intensifying RSC conditions and safeguard oyster aquaculture in this era of unprecedented climate change.