At present, the methods for monitoring the health status of fish mostly utilize blood biochemical indicators. As the blood collection process often causes damage to the fish body (sometimes causing death), the need to develop a noninvasive detection method is urgent. Previous studies have shown that stress indicators can be detected in fish skin mucus or the surrounding water. In this experiment, the level of cortisol in the blood, fish skin mucus, and surrounding water of large yellow croaker was determined at 0, 0.5, 1, 1.5, and 2 h after high-temperature stress induction. Moreover, the levels of malondialdehyde (MDA), immunoglobulin M (IgM), and alkaline phosphatase (AKP) in the serum and fish skin mucus were also measured. The results were as follows: with increasing stress duration, the cortisol levels in the serum, fish skin mucus, and surrounding water increased first and then decreased, all reaching a peak at 1.5 h. The Pearson correlation coefficients for the cortisol levels between the serum and skin mucus, serum and surrounding water, and skin mucus and surrounding water were 0.936, 0.955, and 0.915, respectively, all with a significance level of P < 0.01. The MDA and IgM levels in the serum and fish skin mucus both increased first and then decreased, while the AKP levels in the serum and skin mucus decreased first and then increased. For the MDA, IgM, and AKP levels, the Pearson correlation coefficients between the serum and skin mucus were 0.586, 0.762, and 0.792, respectively, all with a significance level of P < 0.01. According to the results mentioned above, we can use the surrounding water or skin mucus as media to monitor early stress responses in large yellow croaker under high-temperature stress.