Sure. It could very well be sensitive to the load that it is driving. Maybe the high input impedance of the buffer is not loading it the same way other pedals do, causing a difference in the high frequency content.
The clearest example I've ever heard: plug a Fulltone OCD into a true bypass pedal like a delay then use 20 ft of cable from there to the amp. Turn on ocd, play, then turn the true bypass pedal on and off. Very different tone from the OCD depending on how the output is being loaded.