BACKGROUND Postnatal depression is common and negatively affects the mother-baby relationship; oxytocin has been found to have positive effects on parenting behavior. We hypothesize that intranasal administration of oxytocin to mothers with depression will influence their parenting related expressed emotion, creating a better basis for sensitive parenting. METHODS Twenty-five postnatally depressed mothers with infants less than one year participated in a randomized, double-blind, placebo controlled within-subject clinical study in 2011. Mothers attended an out-patient perinatal psychiatry setting in NSW, Australia. They received 24 IU of oxytocin alternating with placebo approximately one week apart in random order, prior to completing outcome measures. The outcome measures were the Five Minute Speech Sample, the Self-Assessment Manikin and the Controlled Oral Word Association Test. RESULTS In the oxytocin condition mothers were sadder (p=.01), and they more often initially described their babies as difficult (p=.038), but they reported that the quality of their relationship with their infant was more positive (p=.036). CONCLUSIONS Despite an adequate sample size to answer our central hypothesis, a larger sample may have elucidated a moderating effect of childhood trauma. CONCLUSIONS Oxytocin did not make depressed mothers happier but their perception of the relationship with their baby improved. Treatment with intranasal oxytocin might show some unwanted side-effects in depressed individuals.