Early detection and intervention of emerging psychiatric comorbidity in serious medical illness is as important as saving the life of a child in critical care. Anxiety disorders, PTSD, and depressive disorders are among the common psychiatric comorbidity that can develop in hospitalized patients or children of hospitalized patients.1,2 Delay or failure in identifying the psychiatric disorders and giving prompt intervention may result in poor treatment outcome and delay in recovery because of possible poor compliance, refusal of treatment, and exaggeration of symptoms. Prevention of deterioration of psychiatric disorder and/or exacerbation of pre-existing mental disorders is a challenge but can be achieved by careful assessment and a comprehensive treatment plan. Any serious or life-threatening medical illness is a crisis in a child’s life and family. It can disrupt the child’s total growth and development—physical, emotional, intellectual, social, and spiritual. The severity and the nature of impact of serious medical illness in children may depend on multiple vulnerability factors that include separation from parents or primary caregiver, developmental age or problems/delay, pre-existing mental disorders, having special needs (e.g., autism, Down syndrome), educational problems (e.g., poor grades, drop-outs), financial difficulties in the family, divorce or separation of parents, parental health, and psychopathology. Several studies indicated that the most common mental disorders in children critical illness survivors were post-traumatic stress disorder (PTSD) (10–28%) and major depression (7–13%).3 The current COVID-19 pandemic with the emerging multisystem inflammatory syndrome in children (MIS-C)4 is expected to increase the prevalence of anxiety and depressive disorders in children in critical care. Stressors like separation from the family and friends, fear and worry about COVID-19 infection, feelings of helplessness, loneliness and boredom, history of violence and child abuse, neglect, and deprivation increase financial problems in the family. Loss of learning time and space for play in school lockdown will predispose children to more psychiatric disorders including risk of suicide, psychotic disorders, and drug and alcohol abuse in adolescents. Using the biopsychosocial model with cultural and spiritual considerations in the intervention of psychiatric comorbidity in children in critical care is essential to ensure effective treatment outcome and prompt recovery. Early collaboration with family or primary caregiver, child psychiatrist, psychologist, therapist, social worker, school counselor, as well as spiritual advisers in the initial, subsequent, and discharge treatment planning or as the need arises will have better prognosis of psychiatric comorbidity and help prevent lifetime impairments and disabilities. The presence and active participation of the mother or her surrogate or significant caregiver in a child’s critical care is a positive and protective factor against the development of psychiatric comorbidity in a child with serious medical illness. Children who are resilient can have positive adaptation despite significant traumatic experiences or adversity. Having a nurturing family relationship with responsive and warm supportive parenting promotes resilience in children and is essential in the prompt and complete recovery of children with life-threatening illnesses and in the prevention of psychiatric comorbidity.