This study examines whether a three-year change in serum albumin concentration is associated with subsequent decline in functional status in older persons. A total of 588 participants from the Longitudinal Aging Study Amsterdam aged 65-85 years were followed for six years. The three-year change in serum albumin was classified in four groups: chronic low (< or =43 g/L at both time points), decrease (decrease of 2.4% or more) from normal to low, decrease but still normal, and stable normal albumin (reference group). During the subsequent three years, absolute change and a decline of one standard deviation or more (termed substantial decline) in functional status was assessed. Functional status was measured in two ways: using performance tests and self-reported functional ability. Substantial decline in functional performance and functional ability was observed in 243 persons (41.3%) and 133 persons (22.6%), respectively. After adjustment for baseline functional status and potential confounders, chronic low albumin and a decrease from normal to low albumin were associated with a greater absolute decline in functional performance and in self-reported functional ability. Using the outcome substantial decline in functional status, only decrease to low serum albumin was associated with decline in functional ability [odds ratio (OR)=1.97; one-sided 95% Confidence Limit (CL)=1.09]. This study indicates that chronic low serum albumin is a determinant of decline in functional status. However, a decrease in serum albumin from normal to low levels but within the normal range was a stronger determinant of future decline in functional status. Change in serum albumin level within the normal range measured between two points in time may be used as a general marker of future functional decline.