Background: Chemo-somatosensory evoked potentials (CSSEPs) elicited by chemical stimulation (CO2 gas) of the nasal mucosa have been shown to be sensitive enough to pick up even weak analgesic effects. With the present study we wanted to investigate whether CSSEPs are also a sensitive tool to capture endogenous pain inhibitory mechanisms elicited by conditioned pain modulation (CPM; where a first conditioning stimulus reduces the sensitivity for a second test stimulus) with a conditioning stimulus of rather low noxious load. Methods: Seventeen healthy participants were tested for CPM effects (conditioning stimulus: tonic heat pain with intensities around the pain threshold induced via a thermode; test stimulus: chemonasal stimulation (73% and 78% CO2)) on CSSEPs and on self-report ratings. Results: We found significant CPM effects in the CSSEPS, with reduced amplitudes and prolonged latencies at several electroencephalogram (EEG) recording positions when using the lower CO2 concentration (73% CO2). In contrast to the visible inhibitory effects on the CSSEPs, subjective ratings of the test stimulus did not reflect CPM action. Discussion: The experimental pain model using CO2 stimuli to elicit CSSEPs proved to be sensitive enough to capture weak CPM effects elicited by a conditioning stimulus of rather low noxious load. The usage of such mild noxious conditioning stimuli-in contrast to stimuli of higher noxious load (e.g., cold pressor test)-has the advantage that the activation of other types of pain inhibitory mechanisms in parallel (like attentional distraction, stress-induced analgesia) can be avoided.