Objectives This study aimed to assess levels of biomarkers associated with inflammation and tissue destruction in peri-implant crevicular fluid (PICF) of implants provided with customized or standard healing abutments during early implant healing. Materials and methods Thirty implants were placed in 22 patients with partial posterior edentulism. Subsequently, test group implants (n=15) received one-piece titanium abutments that were fabricated using computer-aided design/computer-aided manufacturing (CAD/CAM). Control group implants (n=15) were provided with standard abutments. PICF collection and standardized periapical radiographs were carried out at suture removal one week later, following crown delivery after 3 months and at 6 months. Expression of C-reactive protein (CRP), interferon-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12A, IL-17A, macrophage inflammatory protein (MIP)-1α, matrix metalloproteinase (MMP)-13, osteopontin, osteoactivin, Receptor Activator of NF-κB (RANK), and TGF-β were analyzed using a multiplex ELISA kit. Results Both groups showed a significant decrease in protein expression of CRP, IL-1β, IL-6, IL-8, MIP-1α, osteopontin, osteoactivin, and TGF-β, while MMP-13 levels increased during the observation period. A rise in OPG and RANK levels was detected among customized abutments. Expression of CRP was higher, whereas IL-1β, IL-1α, and MIP-1α were decreased in control compared to test group implants after 6 months. Marginal bone loss did not depend on abutment modality. Conclusions Both abutment types showed distinctive temporal expression of inflammatory biomarkers during 6 months following implant placement. Trial registration ISRCTN98477184, registration date 18/05/2022 Clinical relevance Customized healing abutments exert similar effects on inflammation during early implant healing compared to standard healing abutments.