Quantifying mRNA expression, which is heritable and physiologically inducible, reveals biologically important networks and pathways underlying complex traits. Here, we quantify mRNA expression in Fundulus heteroclitus, a small teleost fish, among three populations acclimated to 12°C and 28°C and relate it to variation in six, complex, physiological traits (whole animal metabolism (WAM), critical thermal maximum (CT max), and four substrate specific cardiac metabolic rates (CaM)). Although 366 heart mRNAs and 528 brain mRNAs had significant differential expression between the two acclimation temperatures, none of the mRNA acclimation responses were shared across all three populations in any tissue. Yet, within an acclimation temperature across all three populations, weighted gene co-expression network analyses show that mRNA expression patterns explained WAM, CT max, and CaM trait variation. These analyses revealed 9 significant heart MEs (first principal component of module expression) and 4 significant brain MEs. Heart MEs explained variation in WAM, CT max, and two of the four substrate specific cardiac metabolic rates at 12°C, and CT max at 28C. In contrast, brain MEs explained CT max and WAM at 28°C but not at 12°C. Combining MEs as multiple correlations, 82% of variation in WAM at 12°C was explained by four heart MEs, 80% of variation in fatty-acid CaM at 12°C was explained by three heart MEs, and 72% of variation in CT max at 28°C was explained by three brain MEs. These MEs were enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) terms related to specific metabolic pathways, suggesting that they represent biologically relevant pathways. Together these data suggest that mRNA co-expression explains complex traits; moreover, physiological traits are more reliant on heart expression at 12°C and brain expression at 28°C.