Exposure to particulate matter less than 2.5 microns from either ambient pollution (AMB-PM_2.5) or secondhand smoke (SHS-PM_2.5) have been associated with asthma worsening, but there is little information on effects and relative potency with concurrent exposures. We studied health effects of concurrent exposures to AMB-PM_2.5 and SHS-PM_2.5 over a 6-year period in schoolchildren with asthma. Regression calibration with instrumental variables (RCIV) was utilized to estimate effects of personal exposure to low-level SHS and AMB-PM_2.5 on daily albuterol usage and urinary leukotriene E4 (uLTE₄; a biomarker of asthma-related inflammation) using urine cotinine and concentrations from fixed and personal pollution monitors. Each IQR increase in SHS-PM_2.5 exposure was associated with a 6.7% increase (95% CI: 1.0–12.8%) in uLTE₄ on the same day and 9.4% increase (95% CI: −2.6 to 22.7%) in albuterol use the next day, when children were co-exposed to mean levels of AMB-PM_2.5. The dose-response relationship between health outcomes and one pollutant was higher at lower levels of the other pollutant. For example, at lower levels of predicted SHS-PM_2.5 exposure, increases in health outcomes per IQR increase in AMB-PM_2.5 ranged between 2 and 5%, but were negligible at higher SHS-PM_2.5 levels. Comparing at equivalent co-exposure levels, SHS-PM_2.5 was 1.6 times more potent than AMB-PM_2.5 for uLTE₄ (95% CI: 1.1–2.3); estimates for albuterol usage were similar but less significant. Effects at mean co-exposure levels were closer [SHS to AMB-PM_2.5 potency ratio = 1.2 (95% CI: 0.9–1.5) for uLTE₄ and 1.2 (95% CI: 0.7–1.9) for albuterol usage]. In summary, concurrent exposure to relatively low levels of SHS and AMB-PM_2.5 were associated with health outcomes in asthmatic schoolchildren. Dose responses varied with changes in the relative amounts of each pollutant; SHS-PM_2.5 was observed to be more potent than AMB-PM_2.5 when co-exposure levels were equivalent.