The abundance of the alien, Indo-Pacific damselfish Neopomacentrus cyanomos on an oil-loading platform in the southwest Gulf of Mexico indicates that widely distributed platforms could facilitate the expansion of its geo- graphic range across the western and northern fringes of the Gulf. From there it likely will spread to other areas of the Greater Caribbean. The lionfish example demonstrates that it eventually happens, and can do so rapidly. Reduced temperature effects on the physiology of this species were examined to better predict its survivability in the northern Gulf during winter, when sea surface temperatures fall as low as 15 °C along the coast. Overall, our results show that when the degree of experimental temperature decline was large and rapid, no compensation occurred and the stress response observed mostly reflected cellular processes that minimized damage. Integrated biomarker response values were significantly different between fish rapidly exposed to colder vs. warmer temperatures (declines of −4 °C each day, from 26 to 14 °C), reflected in higher values of blood metabolites and routine metabolic rates observed in fish exposed to 14 and 18 °C respectively, and lower activity of all enzymes, lower protein carbonylation, and higher oxidative damage to lipids in fish exposed to 14 °C. While the phy- siological proxies responded to minimize damage during the rapid-decrease experiment, the same proxies re- flected the consequences of compensation when fish were thermally challenged after a 45 days acclimation at 18 °C. In this case, lower values of blood metabolites and high antioxidant levels and indicators of damages underpinned its pejus lower range. Based on the results of the present work, it seems clear that low winter SSTs in the northern Gulf will slow down the colonization of the inshore area of N. cyanomos. We suggest that the use of physiological cellular stress markers on specimens acquired at the beginning of an invasion should be im- plemented in new standardized experimental protocols, including both rapid increases/decreases of temperature and post-acclimation temperature challenges, to assess the invasiveness potential of aquatic species such as this.