This quantitative study explored the relationships among student-instructor connectedness, learners' anxiety, and motivation in online higher education courses. Research has shown that student-instructor connectedness can affect student motivation in online learning. Utilizing the connectedness and anxiety items of the Student-Instructor Relationship Scale in a large-scale cross-sectional survey with a representative sample of students at a comprehensive research university in the southeastern United States of America, we found significant relationships between the dependent variables (connectedness, anxiety, and motivation). Students with a higher connectedness to the instructor tended to have higher motivation and lower anxiety levels. Additionally, students with higher anxiety levels were more likely to have lower motivation levels. Students perceived a lower level of connectedness with male instructors, whereas male and transfer students had higher levels of anxiety. These findings contribute to the field of instructor connectedness in online learning and have implications for higher education institutions and faculty when considering increasing online learning offerings. We provide recommendations for enhancing student-instructor connectedness in online learning to decrease student anxiety and increase student motivation. [Note: The page range (257-281) shown on the PDF is incorrect. The correct page range is 258-281.]