Compartment syndrome can be a devastating complication with significant morbidity when not recognized or treated expediently. Among the classic pentad of signs and symptoms associated with compartment syndrome, pain that is out of proportion to the injury is often cited as the earliest and most sensitive. We present a case report of an atypical presentation of compartment syndrome of the leg in which a patient taking lithium for bipolar disorder did not report pain out of proportion to the injury mechanism. Lithium has been implicated in altering pain perception and increasing the tolerance and threshold for pain, but this has not been widely reported in the orthopedic literature. In addition to compartment syndrome that was painless, the patient presented with 2 additional atypical findings. She presented with compartment syndrome that was atraumatic and isolated to only 1 out of the 4 compartments of the leg. A compartment syndrome that is painless, atraumatic, and isolated to a single compartment represents an unusual triad of atypical findings that has not been previously reported. With unusual presentations of compartment syndrome, there is an increased risk of late or unrecognized diagnosis, consequently increasing the likelihood of significant nerve damage or muscle necrosis. Clinicians have historically applied a higher level of scrutiny to patients who were deemed “obtunded,” that is, those in whom an assessment of pain cannot be reliably determined. In the past, obtunded patients have included intubated or comatose patients, infants and children, mentally disabled patients, and patients with altered mental status, nerve injury, or distracting injuries. Based on evidence from the psychiatry and anesthesia literatures, we propose that patients taking lithium should be added to this list of “obtunded” patients in whom a reliable assessment of pain may not be possible.