Background: Asthma exacerbations are a leading cause of school absenteeism and time lost from work, affecting the quality of life (QOL) of children with asthma and their caregivers. Objective: The objective of this study was to determine the relationship between measures of asthma severity and the QOL of children with asthma and their caregivers living in rural Saskatchewan. Methods: Data for this research was previously collected in 2005-2007 using a case-control study design. Children were recruited for the case control study following a cross-sectional school based survey of children aged 6-18 years. Cases with physician-diagnosed asthma (n=77) were then selected to examine associations between asthma severity and QOL, with respiratory information collected from a home visit, clinic visit and two-week home monitoring of diurnal peak flow variability (DPV). During the clinic visit, children underwent spirometry and completed the Pediatric Asthma QOL Questionnaire (PAQLQ). During the home visit, parents completed the Child Health Questionnaire (CHQ-PF50) and the Pediatric Asthma Caregiver QOL Questionnaire (PACQLQ) and were given instructions on how to complete the two-week diurnal peak flow home monitoring. Higher mean scores on measures of QOL questionnaires indicated better QOL. Asthma severity was measured by Forced Vital Capacity (FVC), Forced Expiratory Volume in one Second (FEV1), and mean DPV. Linear regression was used to assess the association between the three QOL measures and measures of asthma severity (mean diurnal peak flow variability and percent predicted lung function adjusting for smoking, parental education and asthma medication use in the last 12 months). Results: The lowest QOL score on the PAQLQ completed by the children was being bothered by physical activity (mean = 5.8, standard deviation = 1.19) whereas the lowest mean score on the PACQLQ completed by parents was feeling helpless or frightened (mean = 6.1, standard deviation = 1.28). No significant relationships were found between QOL scales. When the PACQLQ and the PAQLQ were stratified by age groups, parents reported higher mean scores for children in the 13-17 age group (p = 0.01) on the total score of the PACQLQ and activity and emotional subscales (p = 0.003 and 0.03, respectively). No significant correlations were found between spirometry measurements and the three QOL measures. Significant negative correlations were found between mean DPV and the mean PAQLQ Total Score. In a post hoc analysis, examining minimum morning peak flow expressed as percent recent best and QOL, significant positive correlations were found between the minimum morning peak flow measurements and the mean PAQLQ Total Score and Activity subscale. Conclusions: While findings from this study suggest that the CHQ-PF50 could be used to assess emotional aspects of QOL in children with asthma, overall, it may not be a useful tool in assessing the QOL of children with asthma. Peak flow may be a better measure of asthma severity than spirometry when assessing QOL for children with asthma and their parents.