Neutrophils play a pivotal role in both the inflammatory phase and subsequent repair processes, making their activity crucial after contact with biomaterials. Excessive neutrophil activation can lead to complications, including implant rejection, highlighting the importance of modulating their activity. This study investigates the long-term interaction of circulating ovine neutrophils with titanium (Ti) and silicon-doped layer (Si-DLC) coated implants. Additionally, the effects of platelet-rich plasma (PRP), platelet-poor plasma (PPP), and antimicrobial neutrophil crude extract (ANE) on neutrophil activity were assessed. Twelve female sheep were divided into Ti, Si-DLC implant and a control group. Neutrophils were stimulated with PRP, PPP, ovine ANE (oANE), or rabbit ANE (rANE), and their enzymatic activity and reactive oxygen and nitrogen species (RONS) generation were evaluated. Hematological parameters were also analyzed. Results showed no adverse effects at implant sites, and all hematological parameters remained within reference values. Ti and Si-DLC implants did not alter neutrophil activity. PRP significantly increased neutrophil activity and RONS production, while PPP decreased activity. oANE reduced enzymatic activity and RONS generation, indicating potential antiinflammatory effects. rANE showed varied effects on neutrophil function. Both ANEs lacked antimicrobial activity against tested pathogens. This study demonstrates the hemocompatibility of Ti and Si-DLC implants and highlights the potential of blood-derived products in modulating the inflammatory response to implants.