Rhamdia quelen morphophysiological responses to propofol sedation were examined. The purpose was to investigate whether propofol would be a suitable drug to be used in fish transport procedures. Fish were exposed to 0, 0.4 or 0.8 mg L−1 propofol for 1, 6 or 12 h in 40 L tanks, simulating open transport systems. Propofol was able to prevent the peak of cortisol levels experienced by the group exposed to 0 mg L−1 propofol at 1 h. At 0.4 mg L−1, propofol also preserved the stability of hematological (hematocrit, red blood cell count, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration), morphological (red blood cell area), biochemical (cortisol, glucose, lactate, total protein, ammonia, urea, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase) and hydromineral (Na+, Cl− and K+ plasma levels) indicators of stress. Such results suggest that sedation with propofol at 0.4 mg L−1 is suitable for R. quelen transport.