Updated project metadata. Sustained weight loss is the preferred intervention in a wide range of metabolic conditions, but the effects on an individual´s health state remain ill-defined and controversial. Here, we investigate the plasma proteomes of a cohort of 43 obese individuals that had undergone eight weeks of weight loss (average of 12%) followed by a year of weight maintenance. Using plasma proteome profiling, a mass spectrometry-based approach, we measured 1294 plasma samples to examine dynamic changes of hundreds of human plasma proteins, including the entire apolipoprotein family. Longitudinal monitoring of the cohort revealed individual-specific protein levels and functional connected proteins with correlated regulation over time. The wide-ranging effect of losing weight on the plasma proteome was reflected in 93 significantly affected proteins. The adipocyte secreted SERPINF1 and the apolipoprotein APOF1 were most significantly down and up regulated (p<10**13), although their fold-change was modest (-16% and +37%), respectively. Overall, markers of inflammation went down in nearly all study participants (39 of 42), however, there were diverse patterns of inflammation marker responses, allowing individual-specific interpretation of the effects of weight loss. Plasma proteome profiling can be used broadly to evaluate and monitor intervention in metabolic diseases.