This study aimed to measure the levels of GM-CSF, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IFN-γ and TNF-α in peri-implant crevicular fluid (PICF) and saliva from patients with peri-implant disease. Twenty two total edentulous patients were divided into two groups: Mucositis (MU) patients with bone loss around the implants until the first thread and pocket depth ≤3 mm, and Peri-implantitis (PI) patients with at least one implant with bone loss around two or more threads and pocket depth ≥4 mm. The clinical parameters evaluated were probing pocket depth, bleeding on probing, and percentage of plaque. PICF samples were collected from MU sites, and from shallow (SPI) and deep (DPI) sites in PI. Unstimulated whole and parotid duct saliva was collected from all patients. The cytokines were measured by a multiplexed immunoassay. PI patients had a higher percentage of plaque compared with MU (P = 0.02). MU sites had lower pocket depth compared to SPI (P = 0.001) and to DPI (P ≤ 0.001). In PICF, the levels of IL-1β were significantly higher in SPI sites compared to MU (P = 0.03). In the saliva from parotid, IL-8 and IL-12 were significantly higher in patients with PI (P = 0.04). Elevated levels of IL-1β in PICF seem to be a characteristic trait of patients with peri-implantitis. The parotid duct saliva showed a significant increase in expression of IL-8, which might be related to a systemic response.