Stresses on water systems can be quantitatively assessed through indices that account for water demand relative to water availability, e.g., the Water Supply Stress Index (WaSSI). However, as a result of adopting deterministic supply-driven approaches, limited attention is paid to the potential impacts of climatic variability on quantifying water stresses. The current study aimed to account for the impacts of inter-annual and intra-annual variability in the WaSSI stress index and to provide insights into potential opportunities for better water management practices. The results from our analysis indicate that looking only at average stresses can substantially mask the important impacts of climate variability. Louisiana, as a typical example of humid regions in the USA, is subjected to high levels of stresses (WaSSI exceeds 1.0) with higher inter-annual variability in watersheds where thermoelectric power plants exist and extensive water is used for cooling process. In addition, intra-annual variability in some watersheds shows periodicity in terms of seasonal stress distributions due to variability in surface water supply and water demand. Our analysis indicated that the stress variability grows as the median WaSSI increases but up to a certain threshold level and then the variability decreases for very high stress levels. For the annual and monthly scales, the peak variability, quantified as the width of the 2.5-97.5 stress percentiles, reached 68% for a median annual WaSSI of 1.00 and 100% for a median monthly WaSSI of 1.15, respectively. Various decisions related to water use and management can be driven by such variability, at both annual and intra-annual scales. Hence, these results have important implications for applied water resource studies aiming to formulate water management policies and improve water system sustainability under climate variability.