Hippocampus erectus inhabiting the shallow coastal waters of the southern Gulf of Mexico are naturally exposed to marked temperature variations occurring in different temporal scales. Under such heterogeneous conditions, a series of physiological and biochemical adjustments take place to restore and maintain homeostasis. This study investigated the molecular mechanisms involved in the response of H. erectus to increased temperature using transcriptome analysis based on RNA-Seq technology. Data was obtained from seahorses after 0.5-h exposure to combinations of different target temperatures (26 °C: control, and increased to 30 and 33 °C) and rates of thermal increase (abrupt: < 5 min; gradual: 1–1.5 °C every 3 h). The transcriptome of seahorses was assembled de novo using Trinity software to obtain 29,211 genes and 30,479 transcripts comprising 27,520,965 assembled bases. Seahorse exposure to both 30 and 33 °C triggered characteristic processes of the cellular stress response, regardless of the rate of thermal change. The transcriptomic profiles of H. erectus suggest an arrest of muscle development processes, the activation of heat shock proteins, and a switch to anaerobic metabolism within the first 0.5 h of exposure to target temperatures to ensure energy supply. Interestingly, apoptotic processes involving caspase were activated principally in gradual treatments, suggesting that prolonged exposure to even sublethal temperatures results in the accumulation of deleterious effects that may eventually terminate in cellular death. Results herein validate 30 °C and 33 °C as potential upper limits of thermal tolerance for H. erectus at the southernmost boundary of its geographic distribution. © 2022 Elsevier Inc.