High salt (NaCl) intake is considered as a risk factor for osteoporosis. In a metabolic balance study we have recently shown that a very high NaCl intake leads to an increased bone resorption in ambulatory test subjects.Simultaneously, we observed a low-grade metabolic acidosis. To test if high salt intake exacerbates immobilisation induced bone loss ?as we see in space- we conducted a 14-day head-down tilt bed rest (HDBR) study with 8 male test subjects (mean age: 26.3 ± 3.5 years; body weight (BW) 78.0 ± 4.3 kg). They received in a cross-over design a high (7.7 mEq /kg BW per day) and a low (0.7 mEq /kg BW per day) NaCl diet. 24-hour urinary calcium excretion increased significantly in the high NaCl-HDBR intake phase (p = 0.008). High NaCl intake caused an exacerbated excretion of the bone resorption marker C- telopeptide of type I collagen (p = 0.036) in HDBR, accompanied by reduced blood bicarbonate (p = 0.025) and base excess (p = 0.017) levels. However, bone formation marker levels bone specific alkaline phosphatase (p = 0.80) and N-terminal propeptide of type I prokollagen (p = 0.54) in fasting morning blood as well as parathyroid hormone (p = 0.69) did not change. Low-grade metabolic acidosis during high salt intake might be a possible mechanism exacerbating disuse induced bone loss.