Background Blood is the first tissue contacting the implant surface and starting the biological interactions to enhance osseointegration and stimulate bone formation with the progenitor cytokines, chemokines, and growth factors. The coagulation cascade initiates the first step of osseointegration between implant and neighboring tissues. The wound healing may be inadequate unless the blood wets the implant surface properly. Wettability is one of the most important features of the implant surface while lipid level constitutes a milestone that may change the energy of blood, which determines its distribution on implant material. Thus, the aim of this study was to evaluate the effect of lipid component of blood as cholesterol and its treatment on their wetting behavior of titanium surfaces. Methods Five surface groups were formed including grade 4 titanium-machined, grade 4 titanium-SLA, grade 4 titanium-SLActive, Roxolid-SLA, and Roxolid-SLActive. In healthy, hyperlipidemic, and treatment situations, blood was taken from eight rabbits and dropped to the disc surfaces. Contact angles were measured between the blood samples and disc surfaces. Results A significant difference was found between both machined and SLActive surfaces, SLA and SLActive surfaces in the hyperlipidemic period, and only Roxolid-SLA and SLActive surfaces during the treatment period. When evaluated according to time, only grade 4-machined and Grade 4-SLA surfaces showed a significant difference. Conclusions Our findings indicated that each period has its own characteristics and showed the importance of cholesterol in blood structure on applicability of implant surfaces.