Background and Objectives: Interscalene brachial plexus block is often used for surgeries involving the shoulder and upper arm. Known complications include phrenic nerve paralysis, intravascular injection, and cervical epidural block. We report a patient who developed acute hypoxia immediately following this block, presumably secondary to an acute pulmonary thromboembolus (PTE) coupled with phrenic nerve paralysis. Case Report: A 43-year-old man with end-stage renal disease secondary to hypertension was scheduled for primary placement of a left upper extremity arteriovenous fistula. A technically unremarkable interscalene brachial plexus block was performed using a 22-gauge regional block needle and 35 mL of 1.5% mepivacaine. Immediately following injection, the patient's oxygen saturation decreased from 99% to 85%, and he complained of chest pain and shortness of breath and developed hemoptysis. Workup revealed an elevated hemidiaphram, but no pneumothorax or evidence of local trauma. A spiral computed tomogram (CT) suggested acute pulmonary thromboemboli as the etiology of the hypoxia and hemoptysis, although the diagnosis was uncertain. Conclusions: This case report suggests that manipulations and vasodilation related to an interscalene block may have facilitated the dislodgement of a pre-existing upper extremity thrombus.