Background: Because of limited communicative skills, it is not self-evident to measure subjective well-being in people with profound intellectual and multiple disabilities. As a first step towards a non-interpretive measure of subjective well-being, we explored how the respiratory, cardiovascular and electro dermal response systems were associated with the valence dimension of emotion. Material and Methods: Three participants were presented with staff selected negative and positive stimuli. During the presentation we measured the participants' respiration, skin conductance, heart rate and respiratory sinus arrhythmia (RSA). We used behavioural codings as an extra measure of emotional valence. Results: Participants showed a shallow, fast breathing pattern, used less thoracic breathing, had a higher skin conductance and had less RSA when experiencing positive emotions then when experiencing negative emotions. Conclusion: There are physiological differences between positive and negative emotions. The results also indicate that people with PIMD direct their attention away from negative stimuli.