Worldwide, many coastal freshwater ecosystems suffer from seawater intrusion. In addition to this stressor, it is likely that the biota inhabiting these ecosystems will also need to deal with climate change-related temperature fluctuations. The resilience of populations to long-term exposure to these stressors will depend on their genetic diversity, a key for their adaptation to changing environments. Accordingly, this study aimed to understand the long-term effects of salinity and temperature on the population density dynamics of the rotifer Brachionus calyciflorus by considering intra-specific variability. Six clonal lineages of B. calyciflorus, exhibiting differential lethal sensitivity (LC50,24 h) to salinity, were exposed for at least 34 days, to a control and to artificial seawater (at a conductivity corresponding to the LC70,24 h for the most tolerant clonal lineage = 9.89 mS/cm), under three temperatures: 17, 20 (standard) and 23 °C. Long-term exposure to artificial seawater affected population densities, leading to the extirpation of some salinity-tolerant clonal lineages earlier than that of salinity-sensitive lineages. This inversion in short- and long-term sensitivity may suggest a higher susceptibility of populations when exposed to long periods of increased salinity. The negative effects caused by artificial seawater were enhanced at 17 °C and 23 °C, with an even earlier occurrence of extirpation of some clonal lineages, namely, two clonal lineages considered tolerant to artificial seawater. The results suggest the potential synergistic effects of the two abiotic stressors when combined. Overall, a lack of association between the clonal lineages’ short- and long-term sensitivity to salinity or their sensitivity to salinity under different temperature scenarios was observed. These results suggest an increased risk to the resilience of B. calyciflorus populations exposed to climate change-related scenarios of increased salinity and temperature fluctuations owing to an enhanced reduction in their genetic variability.