Facial expressions in prey animals such as equines can convey information regarding their internal state and are therefore often used as cues for welfare and pain evaluation. The state of pain is commonly compared to a neutral state with little consideration given to other experiences that could affect the animal, although this situation is rare outside of experimental contexts. To evaluate the effect of managerial contexts on facial expressions from a nociceptive input, conspecific isolation and sedation with known physiological effects were compared to compound states of nociception. Using an anatomically based facial action coding system and a short acting pain model, patterns of facial activity could discriminate between horses experiencing conspecific isolation, sedation, and a nociceptive stimulus separately. Nociception occurring together with conspecific isolation could not be discriminated from the conspecific isolation alone, and compound nociception and sedation could not be discriminated from control. While blinking frequency demonstrated potential to be a valuable marker when evaluating a nociceptive stimulus in sedated horses, careful consideration must be given to the biological interpretation of facial expressions during situations where managerial or drug effects may be present.