The goal for this study was to evaluate the effects of daily oral intake of a consumable liquid fermentate containing high-molecular-weight hyaluronan, as well as to perform a basic evaluation of safety and tolerability. A randomized, double-blind placebo-controlled study design was used to examine the effects of oral intake of hyaluronan on chronic pain conditions. Safety assessment included a complete blood count with differential, blood chemistry and electrocardiogram. The study duration was 4 weeks, where three tablespoons (45 mL) product or placebo was ingested during the first 2 weeks, and two tablespoons (30 mL) was consumed during the last 2 weeks. Seventy-eight people between the age of 19 and 71 years enrolled, and 72 people completed the study. Statistical analysis was performed using the two-tailed independent t-test for between-group significance and using the paired t-test for within-group significance. A reduction in pain scores was seen after 2 weeks of consumption of both placebo (P<.1) and active (P<.065) product; the reduction was more pronounced in the group consuming the active test product. Using “within-subject” analysis, a highly significant reduction in chronic pain scores was seen after 2 weeks of consumption of three tablespoons of active product (P<.001), whereas only a mild nonsignificant reduction in pain scores was seen in the placebo group. During the reduced intake for the last 2 weeks of study participation, pain scores showed a slight increase. During the last 2 weeks, a significant increase in the quality of sleep (P<.005) and level of physical energy (P<.05) was seen. The pain reduction during the initial 2 weeks was associated with significant reduction in the use of pain medication (P<.05). Consumption of an oral liquid formula containing high-molecular-weight hyaluronan was associated with relief of chronic pain.