Frequent occurrences of extreme weather events, particularly severe temperature fluctuations, have significantly impaired the growth and health of fish and resulted in detrimental impacts on aquaculture production. Despite recognition of the crucial role that temperature plays in aquaculture, there is currently inadequate research to assess the consequences of extreme temperature fluctuations on fish health. Hence, we set up acute warming (AW) and cooling groups (AC) by increasing or decreasing water temperature by 8 °C and then gradually restoring the initial temperature (22 °C), to investigate the adaptive regulation of energy metabolism, immune function, and gut microbiota in largemouth bass (Micropterus salmoides). The fish antioxidant system responded to assist their environmental adaptation: both groups showed activation of serum superoxide dismutase (SOD) and catalase (CAT) secretion, and a significant increase in serum total antioxidant capacity (T-AOC) (P < 0.05). Distinct metabolic strategies were employed to cope with sudden environmental perturbations: upon experiencing a temperature decrease (AC1), largemouth bass exhibited a significant increase in serum triglyceride (TG) and cholesterol (CHOL) levels (P < 0.05), coupled with a reduction in blood glucose levels (P < 0.05). However, a considerable reduction in serum TG and CHOL levels was observed after acute warming stage (AW1) (P < 0.05). Following the recovery of temperature, both groups demonstrated a tendency towards normal energy metabolism (CON). Compared to the AW group, the immune function of largemouth bass in the AC group was dramatically affected: alkaline phosphatase (AKP), aspartate transaminase (AST), and alanine transaminase (ALT) increased significantly, while lysozyme (LZM) decreased significantly when the temperature dropped sharply (P < 0.05). After the temperature fluctuations, there were apparent changes in the gut morphology and microbiota of largemouth bass. Microbial functional analysis using the KEGG database revealed apparent alterations in microbial biological functions, especially during the cooling fluctuation (AC). The results indicated that dramatic weather changes, particularly extreme cold, may be detrimental to the health and welfare of largemouth bass.