Background: The aim of the present study was to report the trajectory of heart rate variability (HRV) indices during a low-grade acute inflammation and their associations to biomarkers for infection. Methods: Twelve patients with uncomplicated acute diverticulitis completed this observational study, which composed of 3 sessions of continuous HRV recording from 9 pm to 8 am during ongoing diverticulitis and at complete remission (baseline). The blood samples were collected at each study session measuring C-reactive protein (CRP) and leukocytes. Results: This study showed that the trajectories of the HRV indices were decreased both in time and frequency domains during acute diverticulitis compared to baseline. In particular, the indices reflecting the balance of sympathetic and parasympathetic activities were affected: standard deviation of normal-to-normal beats (P =003), low-frequency power (P <.001), and total power (P =001). These HRV changes indicate alterations in the autonomic nervous system during acute inflammation. All reductions of mean HRV indices had significant (P <.001) correlations to increased CRP correlations to increased CRP levels during diverticulitis suggesting inflammatory involvement in the observed HRV alterations. Conclusion: We found substantial HRV depression in relation to acute uncomplicated diverticulitis, and this was associated with the elevated CRP levels.