Due to limited data about the impact of lockdown on health status, the present study aimed to investigate the impact of COVID-19-related lockdown on changes in dietary habits, physical activity and serum markers in healthy adults. A total of 38 asymptomatic adults aged from 23 to 59 with a normal BMI (22.5 kg/m2) participated in baseline and post-lockdown measurements that included dietary and physical activity assessment, anthropometric measurements and blood samples; and the lockdown survey which included dietary assessment and questionnaires about changes in lifestyle and physical activity. A decreased diet quality during lockdown was observed (Healthy Eating Index reduced from 64.59 to 61.08), which returned to near baseline post-lockdown. Energy intake decreased during lockdown (p = 0.002) and returned to baseline post-lockdown. Despite lower physical activity levels during lockdown (p = 0.035), we observed no significant changes in body composition. However, we observed a significant increase in serum glucose (p = 0.005), total cholesterol (p = 0.003), and low-density lipoprotein (LDL) (p = 0.049) post-lockdown. Increase in serum glucose levels was pronounced in subjects with higher increase in energy intake (p = 0.039), increased omega-6 fatty acids intake (p = 0.016), those who were exposed to several risky contacts (p = 0.018, compared to those with less risky contacts) and those who were not active in nature (p = 0.008, compared to those active in nature). Increased serum LDL was correlated to decreased monounsaturated fatty acids intake (p = 0.028). Within the limits of this preliminary report, changes in serum markers observed among healthy subjects point to a possible impact of COVID-19-related lockdown on adults’ health to be confirmed in larger groups.