The purpose of this explorative study was, first, to document changes in physiological parameters and behavior observed in dogs following ground transport and, second, to measure the effects on the above variables of a short-term administration of clomipramine, anecdotally already prescribed in private veterinary practice to reduce fear, anxiety, or both. Twenty-four beagles were randomly allocated to either clomipramine (2 mg/kg, q12h for 7 d) or placebo treatment, and then transported 3 times in a truck for 1 hour. Physiological parameters (cortisol, neutrophil:lymphocyte (N:L) ratio, heart rate) and behavior were recorded and analyzed. Clomipramine significantly reduced plasma cortisol (P < 0.05) following transport and tended (P = 0.07) to reduce N:L ratio. Clomipramine tended to only reduce “moving and panting” and drooling. Short-term administration of clomipramine appears to slightly reduce fear, anxiety, or both during transport. More research is needed to confirm the efficacy of this treatment and the appropriate dosage.