Coffee, a popular beverage throughout the world, has been shown to have numerous beneficial health effects, including reducing the risk of developing depression. This effect has only been shown with the consumption of caffeinated coffee and not decaffeinated coffee or caffeine alone and one of many hypotheses attributes this to the loss of key constituents during the decaffeination process. The aim of this study was to investigate whether any of the key bioactive coffee constituents with known anti-oxidant and anti-inflammatory effects are lost during the decaffeination process. The analysis of nine caffeinated and nine decaffeinated samples of various brands and batches of commonly consumed coffee in Australia using HPLC analysis found that, with the exception of caffeine, there were no significant differences in the quantity of other key bioactive coffee constituents in caffeinated and decaffeinated coffee. These results suggest that there may be an alternative explanation for the observed inverse correlation between caffeinated coffee consumption and the risk of developing depression.