ProteinChip is a widely accepted tool for exploring serum pattern profile to evaluate the risk of somatic diseases from different stressors. In this study, by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-ToF), the serum proteome from mice under restraint and thermal stresses were profiled in detail and compared with the control group. Around 150 characteristic peaks were detected in all three groups, with m/z ranging from 1500 to 50,000, with most peaks being within the 2000 m/z to 20,000 m/z range. Compared with the control group, three significant protein peaks with m/z values of 2780, 3303 and 3450 appeared specifically in the restrained stress group and four other peaks with m/z values of 7500, 7811, 29,950 and 38,565 in the thermal stress group. Unexpectedly, no universal positive stress peaks were detected. These preliminary results clearly suggested that there might not be a common mechanism shared by various psychophysiological disorders under different stressors. By fast serum proteomics profiling, SELDI-ToF may be a convenient tool for evaluating the risk of stress-induced illness.