Purpose: The aim of this prospective controlled study was to evaluate the influence of osteopenia on the levels of osteoclastogenesis-related factors in the peri-implant crevicular fluid (PICF) and on the clinical parameters of immediately loaded implants. Materials and Methods: This study included 24 patients who received at least two implants in the mandible, with restorations delivered 48 hours after implant placement. Patients were divided into control (n = 11) and osteopenia (n = 13) groups. Seven days after implant placement (baseline) and 4 months after implant placement, PICF samples were obtained, and clinical parameters (Plaque Index, Gingival Index, bleeding on probing, suppuration, probing depths, clinical attachment levels) were measured. A commercially available enzyme-linked immunosorbent assay was used to analyze PICF samples for levels of soluble receptor activator of nuclear factor of κB ligand (sRANKL) and osteoprotegerin (OPG). At the 4-month follow-up visit, the implant-supported restorations were removed and periapical radiographs were acquired to evaluate bone loss around the implants. Results: Eighty-eight immediately loaded implants were included in this study (38 in the control group, 50 in the osteopenia group). The RANKL and OPG levels, the RANKL/OPG ratio, and the clinical parameters were similar between the groups at both time points. However, the levels of these factors in PICF differed significantly between baseline and 4 months after surgery. Conclusion: Within the limitations of this short-term study, it can be concluded that osteopenia does not influence the PICF levels of osteoclastogenesis-related factors in immediately loaded implants after 4 months of loading. Keywords: dental implants, dental implant loading, immediate loading, osteopenia, osteoporosis, osteoprotegerin, RANK ligand, receptor activator of nuclear factor-kappa B