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In patients with aneurysmal subarachnoid hemorrhage (aSAH), increased brain extracellular interleukin (IL)-6 levels measured by cerebral microdialysis (CMD) were associated with disease severity, early brain injury, delayed cerebral infarction, and axonal injury. In this study, we analyzed brain extracellular IL-6 levels of aSAH patients following parenteral diclofenac. Twenty-four mechanically ventilated poor-grade aSAH patients were included. Changes in cerebral metabolism, brain/body temperature, and CMD-IL-6 levels following intravenous diclofenac infusion (DCF; 75 mg diluted in 100 cc normal saline) were retrospectively analyzed from prospectively collected bedside data (at 1 hour before DCF = baseline; and at 2, 4, and 8 hours after DCF). Statistical analysis was performed using generalized estimating equations. Seventy-two events in 24 aSAH patients were analyzed. Median age was 60 years (interquartile range [IQR]: 52–67), admission Hunt & Hess grade was 4 (IQR: 3–5), and modified Fisher grade (mFisher) was 4 (IQR: 3–4). Higher CMD-IL-6 levels at baseline were linked to fever, higher mFisher, delayed cerebral infarction, and metabolic distress (p< 0.05). CMD-IL-6 levels at baseline were 281.4 pg/mL (IQR: 47–1866) and significantly (p< 0.001; Wald-X2= 106) decreased at 2 hours to 86.3 pg/mL (IQR: 7–1946), at 4 hours to 40.9 pg/mL (IQR: 4–1237), and at 8 hours to 53.5 pg/mL (IQR: 5–1085), independent of probe location or day after bleeding. Parenteral diclofenac may attenuate brain extracellular proinflammatory response in poor-grade aSAH patients.