Background: Acne vulgaris is considered as a persistent inflammatory condition affecting the sebaceous follicles. The strongest inhibitor of sebum production is isotretinoin.. Isotretinoin treatment may cause acquired biotin deficiency by decrease biotinidase activity. The burden of severe acne may be reflected in depression and suicidal thoughts rather than being a side effect of isotretinoin drug. Aim: This work aims to assess the effects of isotertinoin on the biotinidase serum level in acne patients and to correlate these changes with depression and acne scores. Methods: Current study was a randomized control trial study. It included two arms; interventional arm and control arm. Each arm included 22 acne patients aged between 18 and 30 years. Interventional arm received isotertinoin treatment for two months. Level of biotinidase, depression and acne scores assessed before and after the intervention. Results: At baseline assessment, the interventional group showed no statistical significant difference in biotinidsa level, but show a significant higher level of depression score (16.27 ±9.93), versus (10±4.32) in control group with p-value 0.01.The interventional group showed high statistically significant decrease in biotinidase level from (1389.09±499.68) to (716.86±212.18) p-value <0.001 and increase in depression score from (16.27±9.93) to (24.59±12.11) p-value 0.007 after two months. Acne score showed a significant positive correlation with depression score after isotretinoin intake. Conclusion: When isotretinoin is used to treat acne, the biotindase level decreased and the depression score increased.