This cross-sectional study aimed to evaluate the depression and anxiety in pediatric Familial Mediterranean fever (FMF) patients and level of parenting stress in their parents. The study was done on 50 patients with FMF diagnosed according to Tel-Hashomer criteria; and are being followed up at the pediatric Rheumatology clinic, Specialized Children’s hospital, Cairo University and their parents. It also included 50 healthy children coming for regular follow-up, and their parents. Depression was assessed using The Children’s Depression Inventory (CDI), for anxiety The Screen for Child Anxiety-related Emotional Disorders (SCARED) was used, and for parenting stress it was the Parenting Stress Index-Short Form (PSI-SF). Patients included in the study consisted of 60% females with a F: M =1.5:1, and 50 healthy control with a F: M = 1.2:1. Mean age of patients and control were 10.4±2.4 yrs, and 11.1±2.9 yrs respectively. Cases and control were divided according to age into two groups: Group 1 children (6-12 years), group 2 adolescents (13-18 years). Thirteen patients (26%) had consanguineous parents. A positive family history of FMF was recorded in 14 patients (28%). The results of our study indicated that patients with FMF were considerably more depressed and have anxiety scores higher than their healthy peers and it was found that, their parents are having clinically significant stress more than parents of healthy children. Depression scores were 17.8 ± 6.9vs 8.4 ± 4.1 (p = <0.001) and anxiety scores were 30.6 ± 10.9vs 21.4 ± 4.5 (p= <0.001). Parent stress score was 111.0 ± 16.7vs 87.8±10.8 (p=<0.001). There was positive relation between CDI score of depression and age, fever, chest pain, arthralgia & severity score. There was also positive relation between SCARED scores of anxiety and age, fever, chest pain, vasculitis, severity score, response to colchicine, number of attacks in last year and frequency of attacks /month. PSI scores had positive relation with age of patients, fever, chest pain, arthralgia, arthritis, severity score, and number of attacks in last year and frequency of attacks /month. In our study, the most common clinical feature was abdominal pain in (100%) of patients, followed by arthralgia in (98%), fever in (95%), myalgia in (84%) and chest pain in (68%) of patients. Arthritis was found in (68%), erysipelas-like erythema in (32%), and convulsions in (18%) of patients. Disease severity score was mild in 1 patients (2%), moderate in 36 patients (72%) and severe in 13 patients (26%). As for compliance to colchicine, there were (74%) patients who are compliant to treatment and (26%) patients were not compliant. Among the compliant patients, (11%) showed complete response to colchicine and incomplete response was found in (78%) and (11%) of the patients was un-responsive. According to genotypic finding, there were homozygous mutations in 14%, heterozygous in 68% and compound heterozygous in 14% of patients. In our study the most prevalent genotypes were E148Q, V726A & M680I in heterozygous and M694I and M680I in homozygous and the most prevalent genotype in our study as a whole was E148Q. This study showed that levels of depression, anxiety, parenting stress are higher among children and adolescents with FMF and their parents, and suggested that psychosocial assessment of children with FMF has potential clinical implications for the health care needs of these patients and their parents.