The synergic combination of Metronidazole plus amoxicillin has been widely and successfully used for the treatment of aggressive and severe chronic periodontitis, demonstrating additional benefits in clinical and microbiological parameters over scaling and root planning alone. However, and despite its proven efficacy, there is a lack of evidence that evaluates the impact of antimicrobials intake at different times of the mechanical treatment, emphasizing the necessity of a study that compares, simultaneously, the variation of the adjunctive antibiotic effects when they are administered in different moments through the periodontal therapy course.