<p>Anxiety and depression are highly prevalent chronic mental health issues that adversely impact developmental pathways. Evidence indicates that anxiety disorders frequently precede depression in children, while life satisfaction may serve as a protective factor against mental health challenges later in development. This study aims to examine the predictive role of anxiety and life satisfaction to depression, and to investigate the moderating role of life satisfaction in the relationship between anxiety and depression, in a sample of Portuguese school-aged children. Two-hundred and forty-seven children (138 girls and 109 boys), aged between 8 and 10 years (<i>M</i> = 9.06; <i>SD</i> = 0.76), attending grades 2 to 5, answered measures of anxiety (Children’s Manifest Anxiety Scale-Revised), depression (Children’s Depression Inventory), and life satisfaction (Brief Multidimensional Students’ Life Satisfaction Scale). Results showed that elevated anxiety and low life satisfaction were predictors of depression. In addition, a significant moderating effect of life satisfaction on the relationship between anxiety and depression was found. This study adds to the evidence that life satisfaction may be an important protective factor against depression in young children.</p>