Major depressive disorder (MDD) affects a significant number of children and adolescents, yet treatment options for this population remain very limited. Escitalopram (ESC) is one of only two antidepressants approved as treatment for juvenile depression. Still, delayed onset of action, and immediate plus the risk of lasting side effects contribute to low patient adherence, and places the medical prescriber in a difficult situation weighing the potential long-term effects of juvenile treatment against the known consequences of untreated MDD. Research into alternative or augmentation strategies and their long-term effects are needed to improve clinical outcome and better our understanding of the long-term consequences of early-life treatment. We investigated the early-life (postnatal day 35 (PND35)) and lasting (PND60) bio-behavioural effects of pre-pubertal (PND21 to PND34) escitalopram (ESC) administration and/or ω-3 supplementation (OM3) in stress sensitive Flinders Sensitive Line rats. Only ESC treatment showed a strong trend to decrease depressive-like behaviour via significantly increased climbing behaviour on PND35. However, OM3 treatment reduced locomotor activity and increased hippocampal neuroplasticity on PND35, suggesting improved coping behaviour and masking of possible antidepressant-like effects. Reduced locomotor activity lasted into early-adulthood on PND60, despite a treatment-free period from PND35 to PND60. Regardless, early-adulthood antidepressive-like behaviour was only observed in the combination treatment (ESC + OM3) group, despite a significant increase in serotonin turnover, suggesting strong neurodevelopmental process to be involved. Taken together, the combination of ESC and OM3 might induce lasting beneficial neurodevelopmental effects in a stress-sensitive population, suggesting a possible role in current treatment strategies.