Background: Pediatric rheumatic disease (PRD) patients and their caregivers face a number of challenges, including the consequences of the PRD in patients and the impact on multiple dimensions of the caregivers’ daily lives. The objective of this study is to measure the economic, psychological and social impact that PRD has on the caregivers of Mexican children. Methods: This is a multicenter, cross-sectional study including primary caregivers of children and adolescents with PRD (JIA, JDM and JSLE) during April and November, 2019. A trained interviewer conducted the CAREGIVERS questionnaire, a specific, 28-item multidimensional tool validated to measure the impact on different dimensions of the lives of caregivers. Sociodemographic, clinical, and healthcare system data were collected for further analysis. Results: Two hundred participants were recruited (women 169, 84.5%, aged 38 [IQR 33–44] years); 109 (54.5%) cared for patients with JIA, 28 (14%) JDM and 63 (31.5%) JSLE. The healthcare system was found to be determinant on the impact of the disease. The emotional impact was higher in all the participants, regardless of the specific diagnoses. The social dimension showed significant differences regarding PRD, healthcare system, time to reach the center, presence of disability, active disease, cutaneous and systemic manifestations, treatment and partner. Financial and work impacts were more frequent in those caring for JSLE and less so in those with a partner. Family relationships changed in 81 caregivers (25 [12.5%] worsened and 56 [28%] improved). No variables affecting spirituality were found. For caregivers without a partner, the social networks impact increased. Conclusion: The influence of sociodemographic factors can be devastating on families with children with a PRD. These data will help physicians to identify the areas with the greatest need for intervention to achieve comprehensive care for caregivers and their patients.