Background/Objectives: Augmented renal clearance (ARC) may reduce blood concentrations of renally eliminated antibiotics and increase the risk of treatment failure in sepsis. We investigated the risk factors for ARC and the effect of inflammation on ARC duration. Methods: This retrospective cohort study included 282 patients treated for sepsis. The primary endpoint was the ARC incidence, while the secondary endpoints were the relationship between the ARC duration and the time courses of inflammatory marker levels. Patient characteristics, disease severity, laboratory data, and treatment data were collected from medical records. Risk factors for ARC were identified using logistic regression. The effect of the inflammatory response on the ARC duration was evaluated using the Mann–Whitney U test. Results: Among 174 patients (median age, 78 years [range: 29–95]; 94 [54.0%] male; the median intensive care unit length of stay was 6 days [1–76 days]) with ARC identified in 15.5% of patients. Significant risk factors for ARC were age < 75 years (odds ratio, 4.748), albumin levels < 3.0 g/dL (3.672), serum potassium levels < 3.6 mmol/L (5.196), and sequential organ failure assessment scores ≤ 9 (3.803). Patients with an ARC duration of ≥ 8 days had significantly higher white blood cell counts and C-reactive protein levels at ARC incidence than those with an ARC duration < 8 days. Conclusions: Age, albumin, serum potassium, and sequential organ failure assessment scores were risk factors for ARC in patients with sepsis. Persistent inflammation may prolong ARC. These findings can aid in choosing antibiotic dosing regimens based on renal function in patients with sepsis at high risk of ARC.