Lake Sevan is a freshwater reservoir in the Caucasus region. Since the first half of the 20th century, the lake has undergone significant changes caused by human activity and anthropogenic pressure. To identify the current ecological state of two bays—Lchashen and Lichk—located in different parts of the lake, a study was conducted in 2022–2023 using a multi-biomarker approach. For this purpose, biomarkers for assessing the health status of fish and the quality of their living conditions were used such as the activity of acetylcholinesterase (AChE) in the brain, glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and the concentration of reduced glutathione (RGS) and malondialdehyde (MDA) in the liver and gills of the whitefish (Coregonus lavaretus Linnaeus, 1758). In addition, hydrochemical and ichthyological analyses were conducted. This study demonstrated seasonal dynamics for all biomarkers. Comparative analysis of biomarkers and hydrochemical and ichthyological data showed that the whitefish in Lchashen Bay is in worse health, and its living conditions there are less favorable than in Lichk Bay.