In arid environments, perennial rivers are increasingly shaped by anthropogenic flow management and climate variability, leading to the formation of transient isolated pools that serve as temporary refuges for aquatic organisms. We investigated the seasonal influences of biotic (predation) and abiotic (temperature, dissolved oxygen) factors on fish survival in these pools within the Pecos River, New Mexico. Field surveys conducted during the summer revealed that most pools, often created by irrigation dam releases, persisted for less than three days before drying, with extreme heat stress as the primary driver of fish mortality. To assess seasonal variation in survival dynamics, we conducted a mesocosm experiment simulating isolated pool conditions across spring, summer, fall, and winter, manipulating predator access to distinguish biotic from abiotic effects. Our results showed that abiotic stressors overwhelmingly dictated fish survival in summer (high temperatures) and winter (freezing), while predation was the dominant mortality factor in spring and fall, when environmental conditions were less extreme. Notably, avian and mammalian predators, such as herons and raccoons, significantly reduced fish survival in the transitional seasons. These findings emphasize the complex interplay between environmental conditions and species interactions in intermittently available aquatic habitats, underscoring the need to integrate seasonal variability and flow management considerations into conservation strategies. As climate change and human water use continue to alter river hydrology, understanding how fish respond to these shifting pressures is critical for sustaining biodiversity in freshwater systems. This research contributes to the broader field of freshwater science by highlighting the role of seasonality in shaping ecological outcomes, providing insights that can inform habitat management and policy decisions in regulated river systems.