This research aimed to evaluate the salivary concentrations of fluoride (F-), calcium (Ca2+), and phosphate (Pi) after brackets bonding, and to identify the role of [F-], [Ca2+], and [Pi] on the development of active caries lesion (ACL) in individuals under fixed orthodontic treatment. A longitudinal investigation with twenty-two individuals from 11 to 22 years of age was performed in four phases (baseline and after 1, 3, and 6 months). Analyses were carried out considering the salivary concentration of [F-], [Ca2+], and [Pi], as well as the caries index. Data were analyzed using the Friedman test, followed by the Wilcoxon test and the multivariate Cox model (p?0.05). 1 and 3 months after appliance bonding, the [Ca2+] was statistically lower than after 6 months (p<0.0083). On the other hand, salivary [F-] and [Pi] did not show any significant difference during the follow-up. The Cox model demonstrated that the increase of 1 µg/mL in Ca2+ decreased the risk of ACL development by 27%. In conclusion, the levels of Ca2+ changed during orthodontic treatment. A high Ca2+ level in the saliva is a protective factor for ACL development over time.