Acute and chronic emotional distress are associated with an elevated risk of adverse cardiovascular events in humans. However, our understanding of how complex emotional states impact autonomic and cardiovascular regulation in humans remains limited. The purpose of the present case study was to characterize muscle sympathetic nerve activity (MSNA) and peripheral hemodynamic responses to an involuntary mental stress-related lacrimation (i.e., crying) in a healthy, young female participant (age: 22 yr; BMI: 27 kg/m). Continuous heart rate (HR; electrocardiogram), beat-to-beat blood pressure (finger plethysmography), and MSNA (microneurography) were monitored during a 3-min resting baseline and subsequent mental arithmetic task during which an unanticipated and involuntary crying was observed after 1 min of the stress task. Sympathetic and hemodynamic reactivity during the first minute of mental arithmetic were quantified and compared with a retrospective dataset of healthy individuals in whom mental stress reactivity was similarly assessed (31 males, 30 females; age: 21 ± 3 yr; BMI: 25 ± 6 kg/m). Changes in systolic (SBP; Δ3 mmHg) and diastolic (DBP; Δ9 mmHg) blood pressure were comparable with the comparator group (SBP: Δ4 ± 6 mmHg; DBP: Δ5 ± 5 mmHg), whereas HR reactivity appeared slightly higher (Δ32 beats/min) than the comparator group (Δ22 ± 11 beats/min). In contrast, MSNA burst frequency (BF; Δ22 bursts/min), incidence (BI; Δ20 bursts/100 heartbeats), and total area (Δ971%) reactivity were substantially elevated relative to the comparator group (BF: Δ2 ± 7 bursts/min; BI: Δ-3 ± 11 bursts/100 heartbeats; total area: Δ132 ± 285%). These findings suggest that involuntary stress-induced crying is associated with substantial sympathetic activation beyond that observed during standard laboratory mental stress, despite modest changes in hemodynamic variables. The present study is the first to assess muscle sympathetic nerve activity (MSNA) during unanticipated and involuntary stress-induced lacrimation (i.e., crying) in a human. The findings demonstrate that stress-induced crying was associated with what appeared to be a substantial increase of sympathetic nervous system activity that exceeded MSNA responsiveness generally observed in young, healthy adults during acute laboratory mental stress. Exaggerated sympathetic neural reactivity to emotional distress may be one mechanism underlying stress-induced cardiovascular risk.